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Science Supporting Online Material Barios-Rodiles, p. 1 Science Supporting Online Material High-Throughput Mapping of a Dynamic Signaling Network in Mammalian Cells Miriam Barrios-Rodiles, et al. Materials and Methods Development of LUMIER. HEK-293T cells plated in 6-well dishes were manually transfected using the calcium-phosphate precipitation method. After 48 h, cells were lysed as in (S1) and then immunoprecipitated using anti-Flag M2 monoclonal antibody (Sigma). Total protein expression was confirmed by immunoblotting with anti-Smad4 (rabbit) and anti-HA (rat, Roche) antibodies. Luciferase activity in immunoprecipitates and in aliquots of total cell lysates was determined using the Renilla Luciferase Assay System (Promega). For adaptation into the 96-well format, a Multiprobe II Ex 4 Tip (Packard) was used for liquid handling procedures. During development of LUMIER we also examined signal-specific interactions using the BMP pathway and observed increased Smad4-RL bound to Flag-Smad1 but not Smad2, upon activation of BMP signaling (Fig. S1B). LUMIER also recapitulated constitutive interactions such as that between Smad4 and the co-repressor SnoN (Fig. S1C). Construction of the Renilla luciferase-tagged cDNAs. Renilla luciferase tagged baits were generated by PCR, subcloned into pCMV5 and verified by sequencing. Smad4 and TGFβ receptor type I (TβRI-HA) were tagged with Renilla luciferase (AF025846), and the others with a humanized version (AF362545). Smad1, 2 and 3, Smurf1 and Smurf2 were amino-terminally tagged while the receptors, Smad4 and Smad7 were tagged at the carboxy-terminus. Catalytic mutants of receptors and ubiquitin ligases were employed to potentially trap transiently associated proteins, such as substrates, whereas constitutively active versions of receptors were employed to potentially enhance interaction with downstream effectors. Construction of 3Flag-tagged cDNA collection. Approximately 600 cDNAs from the FANTOM1 mouse cDNA library (S2) were manually curated to define the longest open reading frames containing identifiable domains involved in cell signaling (Fig. 2 and Table S2). These cDNAs contained both well-characterized proteins and proteins of unknown function and the library was designed to survey a broad range of signaling proteins, rather than all proteins that contain a single domain class. Of these cDNAs, 95% were successfully amplified using Platinum Pfx polymerase (Invitrogen). The blunt-ended PCR products were purified with the QIAquick gel extraction kit (QIAGEN) and then subcloned into a customized pCMV5-based directional TOPO-vector (Invitrogen) that included an amino-terminal 3X Flag epitope tag (Fig. S2). Eight colonies from each ligation reaction were then screened by PCR and insert orientation and the presence of a stop codon confirmed using a diagnostic EcoRI restriction site incorporated into the reverse primers. DNA from positive colonies was purified using the 96-well format QiaWell kit (QIAGEN). The overall cloning success rate for generating the 3Flag-tagged cDNA set was 77.5%. Twenty-eight in-house Flag-tagged cDNAs were included in the set for the screens and can be identified by their Accession numbers in Table S2.

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Page 1: New High-Throughput Mapping of a Dynamic Signaling Network in … · 2005. 3. 11. · Science Supporting Online Material Barios-Rodiles, p. 1 Science Supporting Online Material High-Throughput

Science Supporting Online Material Barios-Rodiles, p. 1

Science Supporting Online Material

High-Throughput Mapping of a Dynamic Signaling Network in Mammalian Cells

Miriam Barrios-Rodiles, et al.

Materials and Methods Development of LUMIER. HEK-293T cells plated in 6-well dishes were manually transfected using the calcium-phosphate precipitation method. After 48 h, cells were lysed as in (S1) and then immunoprecipitated using anti-Flag M2 monoclonal antibody (Sigma). Total protein expression was confirmed by immunoblotting with anti-Smad4 (rabbit) and anti-HA (rat, Roche) antibodies. Luciferase activity in immunoprecipitates and in aliquots of total cell lysates was determined using the Renilla Luciferase Assay System (Promega). For adaptation into the 96-well format, a Multiprobe II Ex 4 Tip (Packard) was used for liquid handling procedures. During development of LUMIER we also examined signal-specific interactions using the BMP pathway and observed increased Smad4-RL bound to Flag-Smad1 but not Smad2, upon activation of BMP signaling (Fig. S1B). LUMIER also recapitulated constitutive interactions such as that between Smad4 and the co-repressor SnoN (Fig. S1C).

Construction of the Renilla luciferase-tagged cDNAs. Renilla luciferase tagged baits were generated by PCR, subcloned into pCMV5 and verified by sequencing. Smad4 and TGFβ receptor type I (TβRI-HA) were tagged with Renilla luciferase (AF025846), and the others with a humanized version (AF362545). Smad1, 2 and 3, Smurf1 and Smurf2 were amino-terminally tagged while the receptors, Smad4 and Smad7 were tagged at the carboxy-terminus. Catalytic mutants of receptors and ubiquitin ligases were employed to potentially trap transiently associated proteins, such as substrates, whereas constitutively active versions of receptors were employed to potentially enhance interaction with downstream effectors.

Construction of 3Flag-tagged cDNA collection. Approximately 600 cDNAs from the FANTOM1 mouse cDNA library (S2) were manually curated to define the longest open reading frames containing identifiable domains involved in cell signaling (Fig. 2 and Table S2). These cDNAs contained both well-characterized proteins and proteins of unknown function and the library was designed to survey a broad range of signaling proteins, rather than all proteins that contain a single domain class. Of these cDNAs, 95% were successfully amplified using Platinum Pfx polymerase (Invitrogen). The blunt-ended PCR products were purified with the QIAquick gel extraction kit (QIAGEN) and then subcloned into a customized pCMV5-based directional TOPO-vector (Invitrogen) that included an amino-terminal 3X Flag epitope tag (Fig. S2). Eight colonies from each ligation reaction were then screened by PCR and insert orientation and the presence of a stop codon confirmed using a diagnostic EcoRI restriction site incorporated into the reverse primers. DNA from positive colonies was purified using the 96-well format QiaWell kit (QIAGEN). The overall cloning success rate for generating the 3Flag-tagged cDNA set was 77.5%. Twenty-eight in-house Flag-tagged cDNAs were included in the set for the screens and can be identified by their Accession numbers in Table S2.

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Automated imaging. To confirm expression and to obtain preliminary information on subcellular localization of the 3Flag-tagged proteins (Fig. S3), COS-7 cells plated in 96-well dishes were transiently transfected with each clone using PolyFect (QIAGEN). After 48 h, cells were fixed, permeabilized and proteins visualized using an anti-Flag M2 antibody followed by AlexaFluor-488 conjugated goat anti-mouse antibody (Molecular Probes). Images were obtained using the high-throughput ArrayScan II System (Cellomics, Pittsburg, PA) (Fig. S2). Colonies from confirmed clones were pooled into one well of 96-well plate. Working aliquots (5 µL) of 3Flag-tagged cDNAs at 0.02 µg/µL were aliquoted into 96-well plates and stored at –80°C for the LUMIER screens. Detailed information on each 3Flag-tagged cDNA and the subcellular localization of the protein product is available at http://ophid.utoronto.ca/LUMIER/ (S3).

LUMIER automation. The screens (Table S1) were carried out on a ThermoCRS (Burlington, ON) Robotic platform. This platform comprises a Robotics Articulated Arm which runs along a 3 m UMI-33 TRACK system (ThermoCRS), and has access to 14 pieces of equipment mounted on a custom designed table. HEK-293T cells were plated at a density of 22,000 per well in poly-D-lysine coated 96-well plates (COSTAR, Corning) in complete DMEM with antibiotics 24 h before transfection. Cells in the middle 80 wells were transiently-transfected with 100 ng of each 3Flag-tagged cDNA and 125 ng of the Renilla luciferase tagged bait diluted in DMEM without serum or antibiotics using PolyFect (QIAGEN). Negative controls were transfected into the 8 wells of the first column of each plate and were RL-tagged bait in the presence of empty vector. Positive controls (see Table S1) were run in the 8 wells of the last column of each plate. Transfected cells were maintained at 37°C and 48 h later were lysed as previously described (S1). A Multimek 96 (Beckman) liquid handler was used to transfer seventy percent of the cell lysates to a white round-bottom NBS plate (COSTAR, Corning) containing 5 µL of paramagnetic beads (Dynal) coupled to protein G and the monoclonal M2 anti-Flag-antibody (Sigma). Immunoprecipitations were carried out for 1 h at 4°C in a shaker-incubator (ThermoCRS) and the beads washed 8 times using a Biotek ELx405 MAGNA washer with a modified magnetic nest (ThermoCRS). Renilla luciferase activity on the immunoprecipitates was measured in a Berthold Luminometer with the Renilla Luciferase Assay System (Promega). The expression levels of the Renilla luciferase-tagged protein were confirmed in each assay during the screens using ten percent of the total cell lysates. For this, the Dual-Glo Luciferase Assay System (Promega) was used and activity measured in a CCD camera equipped chemiluminescence imaging plate reader (CLIPR, Molecular Devices, CA). Analysis of variance indicated a range between 15-25%, suggesting that the total levels of expression of the RL-tagged proteins did not fluctuate much during the screens.

Biochemical analysis for validation of interactions. For affinity-labeling, HEK-293T cells expressing the TGFβ type I and type II receptors along with the 3Flag-tagged cDNAs were incubated with 250 pM [125I]-labeled TGFβ in media for 1h at 37°C. The receptors were then cross-linked to ligand and immunoprecipitated with anti-Flag M2 antibody as described (S4). For GST-CRIB pull-down assays, affinity-labeled receptors were collected using GST-CRIB as previously reported (S5).

Endogenous interactions. Immunoprecipitations were conducted in mouse mammary epithelial cells (NMuMG) using the antibodies anti-PAK1 (Santa Cruz) and anti-

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Occludin (Zymed). For PAK1-TβRI interactions, cell lysates were subjected to an anti-TβRI immunoprecipitation, using anti-TβRI (V22, Santa Cruz) followed by immunoblotting for PAK1. For endogenous Occludin-TβRI interactions, anti-TβRI immunoprecipitates were immunoblotted for Occludin and to detect TβRII bound to Occludin, Occludin immunoprecipitates were blotted for TβRII (C16, Santa Cruz).

Occludin mutants. 3Flag-Occludin (OCLN) truncation mutants were generated by PCR-based mutagenesis from the wild-type (WT) mouse cDNA. The truncations ∆N53 (1–53), ∆ Tail (275–522) and ∆ CC (422–522) were subcloned in the customized 3Flag pCMV5/TOPO vector. The ∆Loop1(92–127), ∆Loop2(198–237) and Tail(residues 267–522) were subcloned by restriction digestion into 3Flag/pCMV5.

Immunofluorescence. NMuMG cells were transfected with 3Flag-tagged WT or the ∆L1 and ∆L2 mutants of Occludin. After 48 h, cells were washed with PBS and fixed with 4% paraformaldehyde. For cell surface TβRI, cells were fixed and then stained for 1 h at 4°C with rabbit anti-Myc antibody followed by Cy2-conjugated donkey anti-rabbit (green) prior to permeabilization. Following methanol permeabilization 3Flag-tagged Occludin was then detected using anti-Flag M2 monoclonal antibody followed by Cy3-conjugated donkey antibodies against mouse IgG. After washing, ZO-1 was detected using a rat anti-ZO1 (Chemicon) antibody and Cy5-conjugated donkey antibodies against rat IgG. To circumvent cross-reactivity, mouse and rat reagents were used sequentially. The Cy2-, Cy3- and Cy5-conjugated antibodies were purchased from Jackson Immunochemical Laboratories. Imaging was done by confocal microscopy (Leica).

Smad-dependent transcriptional activation assays. 3Flag-Occludin WT and mutants, along with Smad7 were transfected by FuGene6 in NMuMG cells along with 3TP-Luc (S6) and β-galactosidase. The following day, cells were starved with 2% FBS medium overnight and then treated or not with TGFβ for 6 h. Cells were lysed and Firefly Luciferase activity was normalized to β-galactosidase activity.

Data Analysis and Visualization of LUMIER Results LIR calculations. To calculate each LUMIER intensity ratio (LIR), the 8 negative controls (RL-tagged bait in the absence of Flag-tagged prey) on each 96-well plate were averaged. Next, a ratio of the luciferase intensity of each bait (RL-fusions) and prey (3Flag-tagged cDNAs) combination against its corresponding mean negative control was obtained. A linear scaling factor was applied to the LIR dataset for each bait to normalize for variability in the total activity levels of RL-tagged proteins between experiments. Finally, the LIR’s from replicate experiments were averaged to provide the final LIR for each bait-prey combination. LUMIER not only provides qualitative information regarding PPIs, but also conveys semi-quantitative data. However, as we have been unable to identify an assay of sufficient sensitivity to reliably measure the concentration of Flag-tagged protein in our HTP format, we cannot as yet determine affinities. Nevertheless, the LIR value can provide important information regarding the confidence in an interaction and its dynamic regulation by cell signaling pathways. To generate a table of all LIR values (Table S2) each 3Flag-tagged FANTOM1 clone was grouped according to its domain as defined by SMART. We next performed BLAST analysis using the FANTOM1 sequences and the top scoring E value was used to label

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each clone. The corresponding mouse and human Unigene IDs for each clone are also provided in Table S2.

LUMIER assay performance. LUMIER provides semi-quantitative information regarding protein interactions, which can be used to assess confidence that an interaction is real. To evaluate LUMIER performance we first determined reproducibility of the assay by calculating the Pearson’s correlation coefficient for multiple repeated screens of TβRI, Smad2, Smad4 and ALK2. This revealed an average Pearson’s correlation of 0.8. As perfect correlation (i.e. identical data in both screens), would be reflected by a score of 1, this suggests that the screen yields good assay-to-assay reproducibility. To calculate false negative rates in the high-throughput LUMIER data, we comprehensively searched the literature and generated a list of protein interactions in the TGFβ signaling pathway that were tested in our LUMIER screen (Table S3). For an interaction dataset generated from all interactions that had a LIR of more than 1, the false negative rate was low at 17%. When we analyzed the dataset generated from all interactions that had a LIR over 2, the false negative rate rose to 29% and when the LIR cutoff was set to 3, the dataset had a false negative rate of 36%.

False positive rates are difficult to accurately measure, as it is impossible to prove that two proteins do not interact in vivo. However we estimated a technical false positive rate in the LUMIER screen by examining 31 novel interactions with LIRs over 3 using independent secondary assays. For this we employed immunoprecipitation and western blotting using HA tagged TGFβ pathway components and for interactions with TGFβ receptors we also analyzed interaction of Flag-tagged preys with affinity-labeled cell surface receptors. Of these 31 interactions that were observed by LUMIER, 5 were not observed using these secondary assays. This yielded an approximate false positive rate of around 20% for LIRs over 3. Therefore, to generate the TGFβ network graph, we employed a conservative LIR cut-off of 3. To integrate LUMIER results in a network, we used a custom Java-based application to visualize interactions with LIR values greater than 3 (Fig. 3A). Network dynamics (Fig. S5 and Movie S1) were represented using a modification of the Spring-Embedder algorithm, whereby edge lengths were made inversely proportional to the LIR score and the final network adjusted manually to aid visualization of nodes. Edges in the dynamic network were then color coded to reflect LIRs. Overall statistics for each of the baits in the LUMIER screen are presented in Table S4.

Network analysis. The network generated at LIR cutoff of 3 has 947 protein interactions that were detected from 11,914 tests. The degree distribution of the network followed a power-law distribution and appears scale-free (Fig. S4A). Furthermore, the clustering coefficient C(k) of degree k proteins scales as k–1 (Fig. S4B), indicating the network’s hierarchical modularity. The diameter of the network, that is, the average of shortest path lengths over all pairs of nodes, is 2.8, which is close to log(n), indicating the small-world nature of the network. These features of the TGFβ network are similar to those displayed by other PPI networks (S7), as well as other biological (S8) and real-world networks (S9).

Unsupervised clustering using BTSVQ. To identify biologically meaningful information from our PPI dataset, we used Binary Tree-Structured Vector Quantization (BTSVQ), which provides robust unsupervised clustering that is resilient to data pre-processing and normalization, and can extract biologically meaningful clusters from

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complex datasets (S10). BTSVQ combines self-organizing maps (SOMs) and partitive k-means clustering in a complementary fashion. The algorithm can be used for high-dimensional data clustering and visualization, both of preys and baits. To cluster preys, the algorithm partitions data using the standard k-means algorithm in prey space, where k is kept constant at 2. K-means is an algorithm for clustering n data points into k disjoint subsets. First, k random points are defined as cluster centers (seeds). Second, each data point is assigned to the cluster with the closest center. Third, the positions of the k centers are recalculated for each cluster. Steps 2 and 3 are repeated until there are no further changes in the assignment of cluster centers. Iteratively applying the algorithm and using evaluation of variance as a stopping criterion, it thus generates a binary tree. The SOM algorithm is then used to cluster the bait space. To generate SOMs, the SOM algorithm generates best-matching vectors for the bait data (that is, the interaction of each bait with all of the preys) and then randomly distributes them on the map. The SOM neighborhood function then brings baits that have similar interaction profiles with the preys spatially close to each other. For this phase of the clustering, we used a Gaussian neighborhood function with medium radius. Once baits have been clustered, this generates a bait map on the component planes of the SOMs (Fig, 3B). Next, LIR values are overlaid onto the maps to yield SOMs in which each component plane represents one of the 3Flag-tagged proteins used in the screen, and the map unit color reflects the relative LIR values for that protein (that is, the interaction profile of each particular prey with TGFβ pathway component baits) (see Fig. 3C). For each level of the binary tree, the preys are then ranked both with respect to the likelihood of the prey having differential interaction affinity across all baits in the same cluster (called quantization error), and t-statistics. This provides an accurate method of excluding baits with variable interaction affinity across preys, as well as baits with low significance, and thus enables selection of the most differentiating baits between clusters. The cluster structure of the binary tree in prey space is visualized by employing the component planes of the already computed SOM and then preys displaying similar patterns sorted for validation.

Characterization of PAK1 network interactions with the TGFβ receptor. To validate the interaction of the BTSVQ cluster that contained PAK1, we examined the interaction of a selection of the Flag-tagged preys from this cluster with cell surface affinity-labeled TGFβ receptor complexes. This showed a range of interactions with the receptors from weak (Fbx034) to strong (PAK1) (Supp. Fig. S6A). Of note, OSR1, which is a PAK1 interactor, also interacted with receptor complexes. In addition, another component of this cluster, α-PIX, which is a PAK-interacting Cdc42 and Rac1 exchange factor, also associated with receptor complexes, as did the related β-PIX, which interacted with both TβRII and receptor complexes (Fig. S6B). The small GTPases Cdc42 and Rac1 regulate PAK activity and are also activated by TGFβ (S11). Therefore, we extended our analysis to Cdc42, which we showed interacted with cell surface receptor complexes (Fig. S6C). Further, we observed that endogenous receptors bound specifically to a GST-CRIB affinity resin, which binds active Cdc42 and Rac1 (Fig. S6D), suggesting the possibility that endogenous active Cdc42 and Rac may bind to TGFβ receptors. Finally, we examined endogenous interactions using a mouse mammary gland epithelial cell line, and observed endogenous PAK1 bound to endogenous TβRI (Fig. S6E). In addition, we observed endogenous Occludin, another member of this cluster, bound to endogenous TβRI (Fig. S6F). Thus, we define a previously unknown link between TGFβ receptors

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and the PAK network that might suggest a model in which TGFβ receptors regulate PAK signaling by nucleating assembly of a Cdc42, PIX and PAK complex.

Online Access Interaction data and subcellular localization data is available at http://ophid.utoronto.ca/LUMIER/

Figure and Movie Legends Figure S1. LUMIER distinguishes signal-dependent and signal-independent interactions. (A) Schematic of the TGFβ and BMP Smad signaling pathways. See main text for details. (B) HEK-293T cells were transfected with Smad4-RL and Flag-Smad1 or Flag-Smad2 in the presence (black) or absence (white) of BMP signaling. Protein interactions on anti-Flag immunoprecipitates were determined by measuring RL activity. (C) Detection of signal-independent interactions by LUMIER. HEK-293T cells were transfected with Flag-SnoN and Smad4-RL or Smad4-HA and their association detected by LUMIER. RL is driven by the thymidine kinase promoter in pRL-TK and is a negative control.

Figure S2. Construction of the 3Flag-tagged cDNA collection. Manually curated FANTOM1 cDNA clones were amplified by PCR. An example of 96 PCR reactions is shown. The purified bands were subcloned into the customized 3Flag-pCMV5 TOPO vector. Directionality in the vector is provided by the underlined GTGG overhang which hybridizes with the CACC (in red) from the PCR product. The EcoRI site (in magenta) was included in the reverse primer to confirm the presence of the stop codon. Eight colonies per clone were screened by PCR followed by EcoRI digestion. Only cDNAs containing inserts with the stop codon and in the correct direction were subjected to the expression screen by immunofluorescence in COS-7 cells. Six colonies from the same clone, displaying similar subcellular localization are shown as an example. Expressing colonies from the same clone were pooled to perform the LUMIER screens.

Figure S3. Subcellular localization of the 3Flag-tagged set of cDNAs in mammalian cells. COS-7 cells expressing 3Flag-tagged cDNAs were immunostained with anti-Flag M2 antibody followed by AlexaFluor 488-conjugated goat anti-mouse. (A) Hypothetical protein, MGC2941, with a PHD domain localized to the nucleus. (B) Myoneurin, containing BTB and zfC2H2 domains, localized to specific nuclear regions as reported (S12). (C) Rac1 expressing cells showed an increased number of filopodia (S13). (D) FBOXO30 containing a F-box domain is localized to the cytosol. (E) A BTB and Kelch domain containing hypothetical protein, SBB126, displayed a punctate cytosolic pattern. (F) ADP-ribosylation factor 6 localized to the plasma membrane as previously shown (S14).

Figure S4. Network graph parameters. (A) Degree distribution of the TGFβ network. The probability of proteins with degree k [P(k)] is plotted against their degree (k) in a log-log graph. The connectivity of the nodes in the network roughly follows a power-law (scale-free) with an exponent of 1.7. (B) Clustering coefficient of the network. The average clustering coefficient is shown as a function of all nodes of degree k in the network. C(k) approximately follows C(k) ~ k–1 as shown by the fitted line in the graph.

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Figure S5. Dynamics of the Smad subnetwork. The Smad2 and Smad4 network in the absence (left) and presence (right) of TGFβ signaling are shown, with the edge color reflecting the LIR (inset). Note the dynamics of the network (see also Movie S1).

Figure S6. TGFβ receptors associate with members of the PAK1-anchored cluster. HEK-293T cells were transiently-transfected with wild-type or kinase-deficient (KR) TGFβ type I and type II receptors and the indicated Flag-tagged constructs. Cells were affinity-labeled with [125I]-TGFβ and cell lysates subjected to anti-Flag immunoprecipitation (A, B, C) or to GST-CRIB affinity purification (D). (A) Association of Flag-tagged proteins from the PAK1-anchored cluster with TGFβ receptors. Note that CHEK and DUSP3, which are negative in this assay, did not interact with TβRI in the LUMIER screen either and thus were used as negative controls. (B) β-PIX associates with the TGFβ type II receptor and the TGFβ receptor complex. (C) Cdc42 associates with the TGFβ receptor complex. (D) TGFβ receptors may bind active Cdc42. Cells affinity-labeled with [125I]-TGFβ were subjected to GST-CRIB pull-down to allow isolation of proteins associated with GTP-bound versions of Cdc42. (E) Endogenous PAK1 associates with the TGFβ receptor. NMuMG cell lysates were subjected to non-immune (NI) or anti-TβRI immunoprecipitation (α-TβRI) followed by immunoblotting with anti-PAK1. The antibody heavy chain is indicated (IgH). (F) Endogenous Occludin (OCLN) interacts with TβRI. Cell lysates from NMuMG cells were subjected to an anti- TβRI immunoprecipitation followed by immunoblotting with an anti-Occludin (α-OCLN) to detect receptor-associated Occludin.

Figure S7. The TGFβ pathway makes extensive connections to both the PAK1 and polarity networks. The connectivity between the PAK1 (blue) and polarity (green) networks is shown before (A) and after (B) the LUMIER screen with TGFβ pathway components (red nodes), as indicated. Purple nodes are proteins from either network that were present in the LUMIER screen. Nodes connected by black edges represent interactions previously reported in the literature, whereas red edges indicate novel associations unveiled by LUMIER or our directed experiments (see text for details).

Figure S8. Occludin mutants do not affect TGFβ induction of a Smad-dependent reporter gene. NMuMG cells were transiently transfected with the TGFβ-responsive p3TP-Luc reporter in the absence or presence of increasing amounts of WT or the indicated Occludin (OCLN) mutants, or the TGFβ pathway inhibitor, Smad7 (S7) together with a β-galactosidase expression vector to control for transfection efficiency. After overnight starvation, cells were left untreated or were treated for 6 h with TGFβ prior to lysis and measurement of Firefly luciferase and β-galactosidase activities. Luciferase activity for each sample was normalized to β-galactosidase and the results plotted as the mean (+SD) relative luminescence units (RLU) of a representative experiment performed in triplicate.

Movie S1. Dynamics of the Smad subnetwork in the absence and presence of TGFβ signaling. The movie shows the Smad2-Smad4 network in the absence and presence (+TGFβ) of TGFβ signaling, with the LIR value represented by the color of the edge.

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References and Notes S1. P. A. Hoodless et al., Cell 85, 489 (1996). S2. J. Kawai et al., Nature 409, 685 (2001). S3. K. R. Brown and I. Jurisica, Bioinformatics, Advanced Access published on January

18, (2005). doi:10.1093/bioinformatics/bti273. S4. T. Tsukazaki, T. A. Chiang, A. F. Davison, L. Attisano, J. L. Wrana, Cell 95, 779

(1998). S5. E. Vignal et al., J. Biol. Chem. 275, 36457 (2000). S6. H. Hayashi et al., Cell 89, 1165 (1997). S7. S. H. Yook, Z. N. Oltvai, A. L. Barabasi, Proteomics 4, 928 (2004). S8. E. Ravasz, A. L. Somera, D. A. Mongru, Z. N. Oltvai, A. L. Barabasi, Science 297,

1551 (2002). S9. E. Ravasz, A. L. Barabasi, Phys. Rev. E. Stat. Nonlin. Soft Matter Phys. 67, 026112

(2003). S10. M. Sultan et al., Bioinformatics 18 Suppl 1, S111 (2002). S11. S. Edlund, M. Landstrom, C. H. Heldin, P. Aspenstrom, Mol. Biol. Cell 13, 902

(2002). S12. C. Cifuentes-Diaz et al., Muscle Nerve 29, 59 (2004). S13. C. Albertinazzi, A. Cattelino, I. de Curtis, J. Cell Sci. 112 (Pt 21), 3821 (1999). S14. P. J. Peters et al., J. Cell Biol. 128, 1003 (1995).

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IIIIP

P

A TGFβ BMP

P

P

P

P

I II

Smad2/3 Smad1/5/8

Smad4

DNABinding Partner

II

­

15

10

5

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Smad4-RLFlag-Smad1Flag-Smad2 ­­

­­­­­

­­­

++++

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Supplemental Fig. S1 Barrios-Rodiles et al., 2004

- BMP+ BMP

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Colony 6Colony 4Colony 2Colony 1 Colony 3 Colony 5

Clone ING1L

Pool expressing colonies

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TOPO

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Supplemental Fig. S2 Barrios-Rodiles et al., 2004

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Rac1

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A

B

C

D

E

F

ARF6

Supplemental Fig. S3 Barrios-Rodiles et al. 2004

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0.001

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B

Supplemental Fig. S4 Barrios-Rodiles et al., 2004

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LIR> 105 - 103 - 5

SMAD1

OSR1

RAB2B

NRAS

KIS

PAK1

RTDR1

RAB3B

SNARK

UBA52

PPP2R2D

RAB38

PPP2R2B

NEK6

OCLN

PC326

RIT1

STAT1CHEK1

AP2B1

CDC40

NAT8

FBXO30

HDGF

FLJ23360

APBB2

ARL5

ITK

ARHGEF1

ARF4L

CAMK2D

LMO2

GRIP1

SQSTM1

ARHGEF6

ARFRP1

WWP2

RRAS2

SMURF2

SMAD3

ARHGEF11

MAP2K3

WEE1

RHOBTB1

KIAA1115

TRIM35

STK18

ARHG

SFRS16

SMAD2

SMAD4

RIPK2

RIS

UBB RNF14

FLJ13855

GSC

FBXO3

ARL8

RHEBL1

ARFGAP3

RAC2

ARHD

STK35

CXorf9

DKFZp434J0617

RASD2

FBXO34

TOPK

TRIP6

RAB34

ILKAP

STK22C

EIF2AK4

ARHGEF7

RPS27A

ARHJ

RAN

RNF138

LYK5

PLEKHB1

IRAK2

RAB13

RGS3

LHX9

RAB25RAB2B

SMAD1

OSR1

RAB2B

NRAS

KIS

PAK1

RTDR1

RAB3B

SNARK

UBA52

PPP2R2D

RAB38

PPP2R2B

NEK6

OCLN

PC326

RIT1

STAT1CHEK1

AP2B1

CDC40

NAT8

FBXO30

HDGF

FLJ23360

APBB2

ARL5

ITK

ARHGEF1

ARF4L

CAMK2D

LMO2

GRIP1

SQSTM1

ARHGEF6

ARFRP1

WWP2

RRAS2

SMURF2

SMAD3

ARHGEF11

MAP2K3

WEE1

RHOBTB1

KIAA1115

TRIM35

STK18

ARHG

SFRS16

SMAD2

SMAD4

RIPK2

RIS

UBB RNF14

FLJ13855

GSC

FBXO3

ARL8

RHEBL1

ARFGAP3

RAC2

ARHD

STK35

CXorf9

DKFZp434J0617

RASD2

FBXO34

TOPK

TRIP6

RAB34

ILKAP

STK22C

EIF2AK4

ARHGEF7

RPS27A

ARHJ

RAN

RNF138

LYK5

PLEKHB1

IRAK2

RAB13

RGS3

LHX9

RAB25

TGFβsignal

Supplemental Fig. S5 Barrios-Rodiles et al., 2004

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F

OCLN

α-OCLNIB:

IP: Lysa

te

NI α-TβRI

TβRITβRII Auto-

radiography

TβRI + TβRII

PPP1C

PAK1TRIK

Fbx034

STK22D

αPIXOSR1

CHEK−3Flag: −

TβRITβRII

PPP1C

PAK1TRIK

Fbx034

STK22D

αPIX

OSR1

DUSP3

CHEK

IB:α-Flag

Auto-radiography

Total Lysates

DUSP3

IP: α-Flag

Total Lysates

Flag-βPIX

TβRI-HA

TβRII-HIS

IB: α-Flag

Auto-radiography

Flag-βPIX

TβRI-HA

TβRI-HA

TβRII-HIS

TβRII-HIS

IP: α-Flag

­

­

­

­­­ ­

­+

+ + +

+ ++

Auto-radiography

A B

TβRI

TβRIITβRI

Flag-Cdc42

TβRII

TβRII

TβRI

Flag-Cdc42

IP: α-Flag

Auto-radiography

++

+++­

IB: α-Flag

Auto-radiography

Total Lysates

PAK1

α-PAK1

Lysa

te

α-TβRI

NI

IB:

IP:

IgH

E

TβRII

TβRI

GST-Pulldown

GSTGST-C

RIB

beads

Auto-radiography

C D

Supplemental Fig. S6 Barrios-Rodiles et al., 2004

Page 15: New High-Throughput Mapping of a Dynamic Signaling Network in … · 2005. 3. 11. · Science Supporting Online Material Barios-Rodiles, p. 1 Science Supporting Online Material High-Throughput

SMAD4

MARK2

TC10

LGL1/ 2

ZO3

JAM1

MEK5

JAM3

JAM2

PAR3

PATJ

nect in

4.1R

CNX32YES1

ITCHZO1

PAK1IP1

PDPK1

BAD

AKAP11

t au

GSK3B

MAP2K1

SHC1ERBB2

PIK3R1

PAK3

RAF1

MAP3K1

PLCG1

GRB2

PARVB

BMX

SLC12A2

PAR6

OSR1

αPIXGNB3

TGFβR1

Op18

CDC2

DSCAM

SYN1PGAM1 CDK5R1

MYLK FLNA

SMAD2

βPIX

SMAD3

PKCζ/ ι

CDC42/ Rac

AKT1

OCLN

ROCK

CRB3

PALS

SLC12A6

SLC12A1

CBLBCAT1

CAT2

PDGFR

EPHB2

NCK1

RhoA

ZO2

claudin

SMURF1

PAK1

SMAD4

MARK2

TC10

LGL1/ 2

ZO3

JAM1

MEK5

JAM3

JAM2

PAR3

PATJ

nect in

4.1R

CNX32YES1

ITCHZO1

PAK1IP1

PDPK1

BAD

AKAP11

tauGSK3B

MAP2K1

SHC1ERBB2

PIK3R1

PAK3

RAF1

MAP3K1

PLCG1

GRB2

PARVB

BMX

SLC12A2

PAR6

OSR1

αPIXGNB3

TGFβR1

Op18

CDC2

DSCAM

SYN1PGAM1 CDK5R1

MYLK FLNA

SMAD2

βPIX

SMAD3

PKCζ/ ι

CDC42/Rac

AKT1

OCLN

ROCK

CRB3

PALS

SLC12A6

SLC12A1

CBLBCAT1

CAT2

PDGFR

EPHB2

NCK1

RhoA

ZO2

claudin

SMURF1

PAK1

Supplemental Fig. S7 Barrios-Rodiles et al., 2004

LUMIER

A B

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35

30

25

20

15

10

5

0

∆L1 ∆L2– S7 WT

RLU

+TGFβ-TGFβ

NMuMG cells

Supplemental Fig. S8 Barrios-Rodiles et al., 2004

OCLN

Page 17: New High-Throughput Mapping of a Dynamic Signaling Network in … · 2005. 3. 11. · Science Supporting Online Material Barios-Rodiles, p. 1 Science Supporting Online Material High-Throughput

Table S1. LUMIER screens performed. The TGF-β and BMP pathways were activated by overexpressing the TGFβRI (T204D) and ACVR1 (Q207D) receptors respectively.

Screen UniGene ID Interaction partners for positive control

Smad1 Hs. 388294 Smad1+ Flag-Smurf2(C716A) Smad1+ BMP Hs. 388294 Smad1+ Flag-Smurf2(C716A) Smad2 Hs. 110741 Smad2+ Flag-Ski Smad2+TGFβ Hs. 110741 Smad2+ Flag-Ski Smad3 Hs. 288261 Smad3+ Flag-Ski Smad3+TGFβ Hs. 288261 Smad3+ Flag-Ski Smurf1 WT Hs. 436249 Smurf2(C716A)+ Flag-Smad1 Smurf1(C699A) (catalytically inactive)

Hs. 436249 Smurf1(C699A)+ Flag-Smad1

Smurf2 WT Hs. 438968 Smurf2(C716A)+ Flag-Smad7 Smurf2(C716A) (catalytically inactive)

Hs. 438968 Smurf2(C716A)+ Flag-Smad7

Smad4 Hs. 75862 Smad4+ 3FlagSmad2+ TGFβRI(T204D) Smad4+TGFβ Hs. 75862 Smad4+ 3Flag-Smad2+ TGFβRI(T204D) Smad7 Hs. 370849 Smad7+ Flag-Smurf2 (C716A) Smad7+TGFβ Hs. 370849 Smad7+ Flag-Smurf2 (C716A) TGFβRI WT Hs. 28005 TGFβRI WT+ Flag-FKBP12 TGFβRI(K232R) Hs. 28005 TGFβRI(K232R) + Flag-FKBP12 TGFβRI(T204D) Hs. 28005 TGFβRI(T204D) + Flag-FKBP12 ACVR1 WT Hs. 150402 ACVR1 WT+ TGFβRI-Flag ACVR1(K235R) Hs. 150402 ACVR1(K235R)+ TGFβRI-Flag ACVR1(Q207D) Hs. 150402 ACVR1(Q207D)+ TGFβRI-Flag BMPR1B WT Hs. 87223 BMPR1B WT+ Flag-FKBP12 BMPR1B(K231R) Hs. 87223 BMPR1B(K231R)+ Flag-FKBP12 BMPR1B(Q203D) Hs. 87223 BMPR1B(Q203D)+ BMPRII-Flag

Page 18: New High-Throughput Mapping of a Dynamic Signaling Network in … · 2005. 3. 11. · Science Supporting Online Material Barios-Rodiles, p. 1 Science Supporting Online Material High-Throughput

Table S2. LIR Values for TGFβ LUMIER.LIR values for each interaction test are shown. Values between 3-5 are in grey, 5-8 in orange and >8 in yellow.

CloneID Domain Label Mm Unigene Hs Unigene hRL-

SMA

D2

hRL-

SMA

D2+

TGFβ

sig

nal

hRL-

SMA

D3

hRL-

SMA

D3+

TGFβ

sig

nal

SMA

D4-

RL

SMA

D4-

RL+

TGFβ

sig

nal

mSM

AD

7-hR

L

mSM

AD

7-hR

L+TG

Fβ s

igna

l

TGFβ

RI-R

L W

T

TGFβ

RI-R

L (K

232R

)

TGFβ

RI-R

L (T

204D

)

hRL-

SMA

D1

hRL-

SMA

D1+

BM

P si

gnal

AC

VR1-

hRL

WT

AC

VR1-

hRL

(K23

5R)

AC

VR1-

hRL

(Q20

7D)

BM

PR1B

-hR

L W

T

BM

PR1B

-hR

L (K

231R

)

BM

PR1B

-hR

L (Q

203D

)

hRL-

SMU

RF1

WT

hRL-

SMU

RF1

(C69

9A)

hRL-

SMU

RF2

WT

hRL-

SMU

RF2

(C71

6A)

2310047G11 Ras regulation RAN Mm.7521 Hs.10842 0.974 1.589 0.507 0.965 2.126 2.007 0.628 0.652 1.024 1.675 2.138 1.711 1.191 2.051 1.023 1.35 1.461 1.934 1.526 1.414 1.043 0.519 7.6342400004O09 Ras regulation KBRAS1 Mm.264044 Hs.173202 1.61 1.087 0.747 1.453 2.022 1.685 0.721 0.692 4.667 8.097 7.288 2.974 2.367 2.889 6.106 1.616 3.037 3.997 3.842 1.772 1.642 0.964 5.2682600013G09 Ras regulation RABL4 Mm.30191 Hs.415172 1.34 0.84 0.919 1.148 0.902 0.966 0.721 0.561 1.911 2.398 2.99 1.769 1.513 1.351 2.275 0.973 1.402 1.446 1.428 1.304 1.475 1.3 2.4352700023P08 Ras regulation RAB28 Mm.41555 Hs.306899 1.314 0.909 1.215 1.122 1.972 1.676 0.5 0.48 0.95 1.282 0.755 2.202 1.471 0.803 1.065 0.762 0.987 0.961 0.806 1.058 1.123 0.492 1.6332810426G09 Ras regulation ARHG Mm.259795 Hs.75082 1.865 1.705 1.441 2.218 3.856 4.102 0.849 1.063 2.111 2.849 4.647 3.29 2.107 1.75 1.712 1.777 2.209 2.033 1.934 1.563 1.5 0.833 1.6323110035H11 Ras regulation RIT1 Mm.4009 Hs.446472 2.609 4.079 1.528 3.248 1.299 0.913 0.174 0.239 1.611 0.858 2.044 2.627 2.459 1.181 1.663 1.359 1.416 1.047 1.438 2.139 4.806 1.236 0.4613110082B04 Ras regulation RAB11A Mm.1387 Hs.75618 1.336 0.684 0.669 0.876 0.787 0.764 0.555 0.722 0.55 0.58 0.567 1.364 1.098 0.774 0.733 0.828 0.741 0.695 1.502 1.565 1.469 1.111 1.6073732413A17 Ras regulation RAB22A Mm.275304 Hs.281117 0.974 1.752 0.915 1.178 1.929 1.399 0.449 0.528 1.994 2.429 2.288 2.2 1.517 2.574 1.873 1.615 1.51 1.505 1.931 1.54 1.297 2.791 5.1224021402C18 Ras regulation RAP2B Mm.273288 Hs.98643 1.134 1.308 0.609 1.038 0.815 1.005 0.202 0.449 0.93 0.784 2.877 1.876 1.37 1.337 1.079 0.994 1.394 1.334 1.31 1.786 1.154 2.278 0.8794631404I11 Ras regulation RIS Mm.35827 Hs.27018 4.367 3.125 2.252 5.05 4.49 5.417 1.126 0.677 6.196 6.63 6.784 5.564 4.855 2.749 4.747 1.893 2.779 5.063 4.838 2.209 2.732 4.075 2.3454930526B11 Ras regulation RASD2 Mm.179267 Hs.248222 5.237 2.075 1.472 3.319 4.505 2.996 0.704 0.672 4.777 4.047 6.138 4.885 3.973 1.704 3.469 1.653 2.611 2.7 3.178 2.927 3.453 3.308 2.2894930527H08 Ras regulation KBRAS2 Mm.274734 Hs.502910 1.79 1.722 0.849 0.955 1.175 1.194 0.299 0.41 1.441 1.689 1.768 1.726 1.849 0.715 1 0.847 1.061 0.897 0.994 1.561 1.335 1.653 1.5630610007N03 Ras regulation RAB13 Mm.29355 Hs.151536 0.903 1.757 0.609 1.317 3.699 2.532 0.744 0.562 1.848 4.2 3.422 1.948 1.816 2.992 1.779 1.739 1.819 2.383 1.869 2.129 1.198 2.098 3.8440610027H24 Ras regulation RAB17 Mm.279780 Hs.44278 1.117 2.401 0.714 1.688 2.285 2.41 0.264 0.349 2.138 2.782 2.266 2.12 2.166 5.446 1.957 1.93 1.965 2.497 2.79 1.554 1.165 2.154 5.4110610030G24 Ras regulation RAB14 Mm.29302 Hs.5807 1.006 1.019 1.394 1.142 1.14 0.919 0.638 0.669 1.103 0.889 1.278 1.643 1.438 1.541 1.083 1.03 1.01 1.003 1.48 2.017 1.527 1.78 3.2634930544G11 Ras regulation ARHA Mm.73114 Hs.77273 1.822 1.95 1.725 2.488 1.802 2.475 0.729 1.051 3.482 2.619 5.643 2.743 1.969 1.961 1.666 1.768 1.891 2.443 2.348 2.623 2.475 1.597 1.3684931430N23 Ras regulation RAB23 Mm.86744 Hs.94769 1.142 0.656 1.263 0.972 0.587 0.897 0.367 0.423 0.718 0.821 0.786 1.395 0.96 0.898 1.004 0.971 0.886 0.8 0.856 1.737 1.797 0.961 1.2095033421K01 Ras regulation RAB30 Mm.26935 Hs.445862 2.603 2.174 1.129 2.612 2.424 1.774 0.385 0.497 1.903 1.926 2.431 3.632 2.564 1.494 2.306 1.568 1.416 1.256 1.28 2.053 2.436 1.345 1.155730472O18 Ras regulation RALB Mm.27832 Hs.348024 1.179 1.11 1.236 1.034 0.78 1.075 0.235 0.475 1.049 0.908 2.035 2.007 1.378 0.849 0.721 1.1 1.197 0.998 0.729 1.912 1.702 1.188 1.0575830400A04 Ras regulation ARHH Mm.20323 Hs.109918 1.699 1.361 1.207 1.497 1.522 1.44 0.351 0.434 2.784 2.037 3.756 2.446 1.94 1.159 1.397 1.177 2.698 1.602 2.145 2 1.954 1.412 0.8441110001O11 Ras regulation RAB25 Mm.26994 Hs.150826 1.14 2.381 1.325 1.386 4.11 1.812 0.302 0.297 3.427 8.774 5.374 2.172 2.462 4.142 2.322 2.12 1.762 3.717 2.713 0.723 1.245 2.397 4.2141110005O19 Ras regulation ARHJ Mm.27467 Hs.243010 1.79 4.13 1.065 1.707 3.948 3.274 0.435 0.42 2.992 2.934 4.365 2.789 2.501 3.329 3.932 1.51 2.227 3.03 3.105 1.733 1.919 1.463 1.9861300012N20 Ras regulation RAB33B Mm.1664 Hs.191070 2.139 1.906 0.78 2.15 0.969 1.006 0.383 0.437 2.446 4.187 3.331 2.347 1.85 3.115 2.538 1.653 1.955 2.021 2.784 1.758 1.478 2.101 1.5831500012D09 Ras regulation RAB2B Mm.32870 Hs.22399 2.675 2.397 0.912 2.64 4.584 5.589 0.473 0.73 2.216 1.985 2.683 3.39 2.479 2.099 2.284 2.159 1.825 2.106 2.161 1.895 1.761 2.456 2.5395830461H18 Ras regulation RAP2A Mm.261448 Hs.48554 1.565 1.281 1.161 1.893 1.93 2.099 1.072 1.061 4.52 4.892 6.25 3.445 3.116 1.85 4.309 1.774 2.638 3.116 4.096 2.145 2.58 1.974 2.3526330580M05 Ras regulation RAB39B Mm.45148 Hs.24970 1.556 1.225 0.377 1.454 1.07 1.739 0.184 0.579 1.062 1.15 0.973 2.063 1.67 0.849 0.871 0.961 1.1 0.863 0.825 1.625 1.818 1.996 2.2996430710G15 Ras regulation RAB34 Mm.275864 Hs.301853 3.477 3.322 1.907 2.398 2.187 3.205 0.605 0.891 1.529 1.882 3.287 3.152 2.866 1.738 1.257 1.799 1.858 2.331 1.474 1.603 2.086 1.532 2.7691810036J22 Ras regulation RHEBL1 Mm.259708 Hs.159013 3.199 3.039 1.291 2.984 3.779 5.089 0.78 1.368 4.708 8.07 9.14 3.309 3.519 2.266 2.327 3.542 5.045 5.553 5.064 1.639 1.922 2.631 1.4852210410A21 Ras regulation ARHD Mm.27701 Hs.15114 1.818 4.495 1.257 2.521 5.167 4.09 0.889 0.827 2.689 5.031 4.564 2.013 2.034 5.063 1.691 2.242 3.528 4.247 5.022 1.854 2.152 2.074 4.936C330006L04 Ras regulation RAB6B Mm.193647 Hs.352530 2.326 1.456 0.848 2.333 1.883 1.707 0.639 0.677 5.266 7.303 11.48 4.458 3.304 2.794 3.767 1.956 3.016 3.261 5.342 1.895 1.95 2.055 2.1372410015H04 Ras regulation RAB5A Mm.286286 Hs.73957 1.17 0.558 2.058 0.904 1.309 1.094 0.604 0.715 0.738 0.91 0.874 1.569 1.477 1.197 1.144 1.173 0.644 1.078 1.189 1.821 1.152 1.596 1.6352410064E05 Ras regulation RAB9A Mm.25306 Hs.444327 1.181 0.843 0.964 0.87 0.959 1.081 0.391 0.429 1.002 0.998 1.1 0.916 1.367 0.964 0.978 1.064 1.097 0.906 1.251 1.298 1.14 1.029 1.3132510038J24 Ras regulation RAC2 Mm.1972 Hs.301175 2.714 2.777 2.266 2.151 4.528 6.363 0.407 0.565 2.579 2.517 2.989 3.03 2.511 1.339 1.811 1.617 1.988 2.005 1.662 1.685 1.789 1.519 1.4522610017M01 Ras regulation ARHE Mm.46497 Hs.6838 0.852 0.916 0.72 0.688 2.144 2.217 0.159 1.485 0.866 1.023 1.201 1.504 1.46 1.027 0.85 1.377 0.935 1.007 1.963 1.445 1.4 1.125 2.8392610037B10 Ras regulation NRAS Mm.256975 Hs.260523 1.641 1.994 1.402 1.091 3.743 3.375 0.765 0.591 1.752 2.171 1.463 1.303 1.384 6.657 1.622 2.995 1.668 2.332 2.244 1.822 1.317 1.608 6.0852610100O16 Ras regulation RAC1 Mm.292510 Hs.413812 1.198 1.149 0.856 1.365 1.746 1.075 0.266 0.516 1.43 1.173 1.221 1.841 1.477 2.546 1.292 1.703 1.283 1.153 0.673 2.581 1.388 1.551 3.7212610528C18 Ras regulation RAB3B Mm.41580 Hs.123072 2.295 2.585 1.286 2.204 3.325 4.044 0.658 0.66 2.623 4.218 4.33 3.252 2.684 3.799 3.21 2.431 2.388 2.52 2.171 1.61 1.271 2.95 1.4192700008D04 Ras regulation MEL Mm.162811 Hs.5947 0.698 0.852 0.324 0.644 0.508 0.79 0.35 0.357 1.874 1.798 2.108 1.47 1.196 1.14 1.077 1.179 1.143 1.178 1.198 1.354 1.034 1.213 1.1012310011F14 Ras regulation RAB38 Mm.276669 Hs.108923 3.689 2.872 2.233 3.271 5.398 7.266 0.918 1.425 3.756 4.483 5.392 3.31 3.24 2.372 2.849 2.444 3.758 4.375 2.567 1.761 1.846 2.481 1.9353110037E15 Ras regulation RAB3C Mm.151600 Hs.184691 1.037 0.849 0.696 0.621 0.942 2.592 0.404 0.576 1.196 1.227 1.682 1.304 1.182 1.094 0.925 1.457 1.217 1.047 0.833 1.434 1.106 1.542 1.5680610007B10 Ras regulation CDC42 Mm.1022 Hs.355832 1.156 0.804 0.914 0.648 1.348 1.282 0.93 1.08 0.972 0.816 2.362 1.492 1.133 1.199 0.862 1.585 1.35 0.734 0.93 1.342 1.378 2.562 1.6572610016H24 Ras regulation RRAS2 Mm.276572 Hs.206097 0.982 1.806 3.251 1.632 6.779 9.353 0.643 0.821 1.077 2.065 1.997 2.397 1.947 4.138 1.242 2.126 2.059 3.131 1.388 1.684 1.304 1.85 4.7141300014J11 Ras regulation RAB7 Mm.298257 Hs.356386 1.54 0.9 0.42 0.125 0.812 0.872 1.065 1.041 0.867 0.678 0.689 1.551 1.377 1.103 0.752 1.026 1.086 0.843 0.38 1.415 0.905 1.661 2.0251700008H16 Ras regulation RHOBTB1 Mm.31108 Hs.15099 3.908 1.418 1.804 0.501 1.558 1.18 0.762 0.739 4.922 5.548 8.617 2.618 3.475 2.094 3.157 2.16 3.278 3.419 5.549 3.893 6.984 2.425 1.0231700009N14 Ras regulation RAN Mm.23522 Hs.10842 3.401 1.985 2.774 2.497 2.967 2.822 0.467 0.634 3.298 6.143 4.957 3.199 3.015 1.929 2.779 1.968 2.267 3.03 3.043 1.839 1.672 2.824 1.8941700025K02 Ras regulation RAN Mm.103632 Hs.10842 2.802 1.176 0.899 1.838 1.76 2.983 0.564 0.697 4.464 5.258 7.941 3.984 3.839 1.813 2.723 2.229 2.73 3.01 4.607 1.761 1.665 1.48 1.6011810035F16 Ras regulation ARFGAP3-v2 Mm.286911 Hs.13014 1.024 0.968 1.525 0.285 1.117 0.932 0.619 1.005 0.553 1.003 0.626 1.759 0.795 0.883 0.885 1.127 0.887 0.91 0.907 1.213 1.335 0.77 0.9522310032E02 Ras regulation ZNF289 Mm.43636 Hs.436204 1.639 1.378 2.715 0.551 1.284 1.504 0.825 1.411 1.391 2.018 1.583 1.782 0.87 1.917 1.511 1.77 1.674 1.025 1.657 2.598 2.388 1.204 1.2492310075M19 Ras regulation GNAI2 Mm.196464 Hs.77269 1.233 1.256 1.38 0.358 1.459 1.069 0.655 0.782 1.913 2.08 1.832 1.994 0.919 1.72 1.98 1.588 2.078 1.673 2.424 1.444 1.251 0.527 0.6092310075M17 Ras regulation SARA2 Mm.196592 Hs.279582 0.52 0.604 0.389 0.13 0.414 0.791 1.181 1.368 0.886 1.478 0.849 1.163 0.45 1.619 1.486 1.375 0.893 0.901 1.378 1.178 0.502 0.543 0.479A930014M17 Ras regulation DKFZp761H079 Mm.96833 Hs.369885 1.902 1.445 1.7 0.531 1.168 1.822 0.662 0.825 3.76 6.588 3.907 3.876 1.603 1.883 3.638 2.139 2.96 4.693 2.922 2.868 1.562 0.743 2.6229130014L17 Ras regulation FLJ22595 Mm.98122 Hs.287702 1.655 1.968 0.582 0.405 0.898 1.187 0.296 0.454 2.742 2.667 1.756 1.751 0.944 0.8 1.736 0.987 1.506 1.23 0.986 3.133 2.982 0.84 1.542610009M23 Ras regulation SNX15 Mm.21071 Hs.80132 0.835 0.668 0.662 0.15 0.916 1.1 0.279 0.479 0.755 0.74 0.741 0.968 0.452 0.708 0.634 0.791 0.734 0.601 0.619 1.42 0.75 0.903 1.3471700025P09 Ras regulation ARF6 Mm.318195 Hs.89474 0.741 0.612 0.291 0.135 0.628 0.873 0.442 0.583 0.5 0.765 0.295 1.018 0.42 0.742 0.579 0.817 0.601 0.597 0.569 0.913 0.747 1.463 0.691110018H24 Ras regulation MINA53 Mm.255635 Hs.23294 1.422 1.176 1.246 0.394 2.399 1.973 0.689 0.716 1.678 2.327 1.248 2.037 0.887 1.5 1.319 1.241 1.445 1.669 1.474 1.734 1.807 1.568 0.9782410015N24 Ras regulation ARL5 Mm.280257 Hs.342849 1.26 1.379 1.14 0.589 5.032 2.786 0.497 0.793 1.986 3.821 1.515 3.359 1.039 1.628 1.377 1.189 1.301 1.89 1.538 1.652 1.442 1.479 0.9411500006I01 Ras regulation ARFRP1 Mm.87720 Hs.389277 1.177 0.983 1.181 0.37 3.888 1.416 0.811 0.961 1.718 2.128 2.25 2.317 0.957 1.258 0.949 1.566 1.557 1.429 2.085 1.76 1.593 1.056 0.8731700023N04 Ras regulation ARL4 Mm.12723 Hs.245540 1.195 1.07 1.513 0.343 2.309 1.328 0.963 1.178 1.25 1.739 1.472 1.883 0.754 1.393 1.086 1.316 1.01 1.32 0.727 1.6 1.506 1.371 0.8844930587A11 Ras regulation ARL8 Mm.174068 Hs.25362 0.872 1.444 0.846 0.493 4.53 3.217 0.53 0.63 1.269 1.96 0.983 2.587 0.946 1.352 1.375 1.304 1.364 2.204 0.845 1.544 0.943 0.867 2.3854632412M04 Ras regulation RGS12 Mm.196208 Hs.434933 1.069 1.586 2.013 0.791 2.123 2.327 0.834 1.122 1.332 2.183 1.984 1.664 0.952 1.804 2.118 1.933 1.601 2.287 1.056 1.971 2.311 0.068 2.4392610313E07 Ras regulation FLJ10702 Mm.271178 Hs.277255 2.406 2.067 1.497 0.777 2.481 2.179 0.571 0.81 3.131 2.099 2.68 2.756 1.381 0.949 1.478 1.627 1.548 1.494 1.548 1.977 1.965 0.951 0.8641110036H21 Ras regulation ARF4L Mm.266840 Hs.183153 2.6 3.174 2.175 0.988 1.9 1.326 0.487 0.538 5.246 5.759 3.962 3.31 1.571 1.056 2.631 1.747 2.282 2.469 2.29 7.11 5.744 1.255 0.724

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2310008D22 Ras regulation ARL1 Mm.291247 Hs.372616 1.393 0.929 2.12 0.437 2.15 2.36 0.583 0.495 1.482 2.007 2.158 2.345 0.859 1.385 1.189 1.495 1.563 1.335 1.234 1.994 1.366 1.219 0.5585830420E16 Ras regulation GIT2 Mm.195632 Hs.418057 0.922 0.71 1.141 0.252 1.013 0.775 0.995 0.833 2.8 4.659 2.71 1.828 0.821 1.469 1.948 1.698 1.335 1.295 1.526 2.069 1.272 1.887 0.5454921525H11 Ras regulation SMAP1 Mm.196452 Hs.410882 1.27 1.23 1.783 0.242 1.038 1.783 0.784 1.166 0.42 0.724 0.952 1.317 0.691 0.931 0.715 1.25 1.262 1.308 1.466 1.833 0.907 1.824 3.1751810004P07 Ras regulation ARFGAP3-v1 Mm.286911 Hs.13014 1.914 3.316 1.588 0.715 1.927 2.216 0.305 0.512 1.632 1.632 1.169 1.811 0.989 1.343 2.025 1.718 1.458 1.282 0.904 2.108 1.867 0.077 1.3981200003G10 Ras regulation GNAI3 Mm.271703 Hs.73799 1.328 1.143 1.409 0.351 0.752 0.995 0.343 0.532 1.36 1.727 1.462 1.793 0.855 0.79 1.275 1.002 1.29 1.217 1.212 2.075 2.229 0.793 0.9462610200H14 Ras regulation GNA13 Mm.193925 Hs.9691 1.142 0.897 1.272 0.376 0.921 0.963 0.214 0.87 1.344 3.123 1.276 1.807 1.002 0.959 1.508 1.23 1.025 1.073 1.097 2.836 2.277 1.345 0.8170610037B21 Ras regulation GNG11 Mm.25547 Hs.83381 1.042 0.969 0.9 0.409 1.343 1.166 0.935 1.178 1.8 1.567 2.763 1.705 0.952 1.626 1.417 1.54 1.143 1.278 0.941 3.438 2.72 1.48 1.003A930015K11 Ras regulation GNGT1 Mm.95398 Hs.73112 1.023 0.955 1.332 0.292 1.96 1.505 0.199 0.735 0.977 1.128 0.748 1.359 0.831 1.252 0.903 1.215 0.819 0.821 0.83 2.215 1.914 1.565 0.8731500031D04 Ras regulation GNG13 Mm.218764 Hs.247888 0.853 0.785 0.922 0.206 1.332 1.388 0.859 1.019 0.649 1.549 0.631 1.377 0.605 1.001 1.075 1.528 1.042 1.02 1.322 2.473 1.464 1.622 0.7682410018N20 Ras regulation GNGT2 Mm.46299 Hs.181781 1.1 0.826 0.755 0.277 1.788 2.005 1.071 1.517 0.769 0.725 0.85 1.667 0.936 1.535 0.712 1.491 0.865 0.754 0.785 2.028 1.257 2.438 1.4111110008L10 Ras regulation GNG2 Mm.41737 Hs.112928 0.932 1.223 1.389 0.304 0.913 1.91 0.89 1.236 1.393 1.954 1.341 1.217 0.654 1.255 1.155 1.528 1.149 1.262 1.11 2.015 0.887 1.213 3.5451190002P14 Ras regulation GNG3 Mm.27307 Hs.179915 1.007 1.247 1.145 0.255 1.261 1.809 0.472 0.861 1.471 2.3 1.392 0.94 0.643 1.161 1.278 1.388 1.031 1.058 0.685 1.939 1.431 0.826 2.3761600029K01 Ras regulation GNG12 Mm.13080 Hs.8107 0.943 1.45 0.887 0.354 0.72 1.116 0.398 0.399 1.194 1.07 1.004 1.114 0.786 0.693 0.788 1.116 0.879 0.611 0.835 2.775 1.996 0.819 0.7970710005M12 Ras regulation 0710005M12 Mm.254898 Hs.443810 1.454 1.047 1.461 0.291 0.781 1.658 0.674 0.686 0.787 0.842 0.615 1.581 0.876 1.049 0.72 1.111 0.554 0.797 0.325 2.035 1.44 0.753 1.1235830418G11 Ras regulation RALGPS1A Mm.274249 Hs.432842 1.445 0.979 0.905 0.324 1.346 2.407 0.677 0.648 1.546 2.095 1.03 1.65 1.117 1.088 1.437 1.334 0.686 1.2 1.18 2.841 1.65 1.051 1.3691300003D20 Ras regulation RGL3 Mm.110594 Hs.375142 0.438 0.452 0.584 0.118 0.22 0.386 0.297 0.266 0.395 0.518 0.392 0.857 0.395 0.772 0.468 0.923 0.589 0.559 0.409 1.559 0.792 0.56 0.4585830477L08 Ras regulation CDGAP Mm.268397 Hs.300670 1.103 1.036 1.005 0.341 0.965 1.035 0.513 0.625 3.153 3.513 2.637 2.125 1.108 1.866 1.907 1.667 1.905 1.905 2.159 3.351 1.703 0.883 1.2223110043J09 Ras regulation 3110043J09Rik Mm.128411 1.289 2.111 0.353 0.408 0.999 0.947 0.395 0.461 0.775 0.97 0.907 1.331 0.746 0.964 0.697 1.055 0.66 0.822 0.724 1.949 1.446 0.978 2.3821700026N20 Ras regulation CHN2 Mm.253127 Hs.407520 1.998 1.037 1.577 0.543 2.056 1.315 0.516 0.975 3.121 5.197 3.073 1.754 1.066 1.061 2.927 1.937 1.206 1.887 1.702 2.088 2.273 1.055 1.3411200004L23 Ras regulation INPP5B Mm.296202 Hs.449942 2.271 1.193 1.695 0.481 2.003 2.024 0.608 0.81 1.598 1.734 1.62 1.635 1.067 2.235 1.751 2.128 1.389 1.527 1.625 2.819 3.213 1.376 1.325133400C09 Ras regulation BCR Mm.182202 Hs.446394 2.174 1.813 1.43 0.514 2.254 0.936 0.476 0.62 3.952 3.891 3.202 2.743 1.755 2.154 2.546 2.417 2.966 1.914 3.663 2.736 2.277 0.824 0.5210710001E19 Ras regulation CHN1 Mm.257073 Hs.380138 1.584 1.231 1.721 0.383 2.875 2.093 1.199 1.056 6.025 12.13 5.445 1.571 0.918 3.145 4.248 2.384 2.054 2.51 3.724 2.198 1.605 1.182 0.9914933411B03 Ras regulation ARHGAP19 Mm.21646 Hs.80305 1.619 1.58 1.319 0.548 1.217 1.571 0.58 0.6 0.965 0.712 0.902 1.344 0.852 1.182 1.319 1.388 1.092 1.219 1.067 2.583 2.503 0.753 1.9331700006A11 Ras regulation 1700006A11Rik Mm.158761 1.249 0.832 1.512 0.367 1.394 1.735 0.87 1.186 2.297 2.526 1.51 1.468 0.854 1.917 1.5 2.502 1.47 1.592 4.362 1.93 1.602 0.792 0.8752610528A06 Ras regulation ARHGEF1 Mm.3181 Hs.278186 2.435 3.176 0.969 2.628 2.745 2.262 0.679 0.807 1.077 1.524 1.421 1.751 1.979 1.032 1.169 0.703 0.651 0.851 0.725 3.68 3.017 3.434 0.4624833419J07 Ras regulation ARHGAP18 Mm.276368 Hs.413282 1.782 2.218 0.803 1.168 2.716 1.341 1.238 1.092 1.388 2.586 0.966 1.206 1.665 1.121 1.182 1.322 1.15 1.316 1.204 2.144 2.811 1.208 0.528KIAA0380 Ras regulation ARHGEF11 Mm.179723 Hs.371602 1.222 1.989 1.988 1.758 3.095 1.368 1.665 1.31 1.821 1.263 1.018 1.596 1.553 1.169 1.046 1.469 0.885 0.993 1.283 4.606 1.903 1.266 1.091NM_145735 Ras regulation ARHGEF7 Mm.244068 Hs.172813 3.2 3.383 3.481 3.866 6.268 2.6 0.728 0.901 1.169 1.318 1.078 4.226 5.348 1.239 1.003 1.404 1.132 1.279 0.839 2.689 3.625 0.781 0.163AY014180 ubiquitination SMURF2-WT Mm.200086 Hs.438968 6.364 5.818 1.497 5.988 0.673 0.736 0.642 0.751 0.636 0.64 1.339 27.6 26.97 0.91 0.685 0.824 1.25 0.712 0.463 1.34 0.97 1.36 0.893AY014180 ubiquitination SMURF2(CA) Mm.200086 Hs.438968 8.733 9.893 2.277 13.02 0.869 1.125 8.813 9.065 0.913 0.758 0.724 32.46 67 1.05 0.905 1.146 1.52 1.02 0.313 1.101 1.324 0.998 1.514XM_166483 ubiquitination SMURF1-WT Mm.27735 Hs.436249 0.638 0.858 0.476 0.492 0.208 0.288 0.132 0.186 0.537 0.346 0.839 1.182 0.954 0.986 0.472 0.75 0.678 0.644 0.456 1.685 1.343 1.044 0.79XM_166483 ubiquitination SMURF1-CA Mm.27735 Hs.436249 1.517 2.787 0.637 1.457 0.503 0.521 0.665 0.532 0.57 0.426 0.649 5.601 14.48 0.834 0.863 0.823 0.671 0.837 0.928 1.729 1.151 0.887 1.3094930511O11 ubiquitination 4930511O11Rik Mm.79212 Hs.498027 1.36 1.41 1.496 0.486 0.883 1.246 0.835 0.942 1.401 2.081 1.821 2.096 0.913 1.61 1.099 1.515 1.181 1.476 1.622 2.816 1.589 0.658 2.0244930455J02 ubiquitination LOC51035 Mm.27839 Hs.351296 2.257 1.771 1.696 1.214 2.156 2.659 1.832 1.312 4.34 2.01 4.719 1.539 3.775 3.458 3.272 2.295 3.387 2.929 3.056 2.853 3.614 2.487 1.1292700092A01 ubiquitination UBAP1 Mm.289795 Hs.436169 0.874 0.739 1.028 0.549 1.612 2.696 2.118 0.996 0.621 1.001 0.84 1.224 1.131 1.156 1.506 1.109 1.332 0.899 1.323 1.475 1.718 1.394 0.6988030447B05 ubiquitination HIP2 Mm.263318 Hs.246603 0.91 0.621 0.613 0.276 1.232 2.032 1.553 0.688 0.646 0.47 0.574 1.134 1.14 0.86 1.295 0.7 0.887 0.72 1.143 1.403 1.249 1.292 0.632510040N03 ubiquitination UBL1 Mm.259278 Hs.81424 1.446 0.772 0.676 0.417 1.044 1.663 1.166 0.706 0.781 0.952 1.543 1.123 1.204 0.923 0.829 0.839 0.827 0.918 1.081 1.143 0.79 1.434 1.1973000008M07 ubiquitination UBB Mm.282093 Hs.356190 2.068 2.175 1.224 1.402 1.654 3.094 0.862 0.524 3.942 1.115 3.817 1.63 2.256 1.266 1.489 1.797 2.584 1.495 2.602 4.37 2.568 2.26 1.2980610006J14 ubiquitination RPS27A Mm.180003 Hs.311640 3.721 3.57 2.231 2.662 2.837 3.381 1.777 1.345 9.051 4.818 11.66 2.768 5.144 5.358 4.998 6.351 5.615 5.652 11.13 5.837 4.027 2.793 2.1880610008O06 ubiquitination FAU Mm.298117 Hs.387208 1.305 1.567 1.232 0.52 2.277 1.656 0.556 1.383 1.71 0.613 0.772 1.201 1.308 0.966 0.793 1.351 1.553 1.037 1.511 1.569 1.636 1.233 1.9361200014H24 ubiquitination SF3A1 Mm.190766 Hs.406277 0.818 1.018 1.113 0.579 1.104 0.728 0.488 0.94 0.644 0.589 0.572 1.311 1.574 1.145 1.206 1.156 1.144 0.884 0.747 2.432 3.036 1.341 1.1242010309G22 ubiquitination UBD Mm.140210 Hs.44532 1.761 1.085 1.156 0.675 1.233 2.571 1.518 1.078 3.762 2.667 4.413 1.309 2.43 1.094 2.218 1.205 1.566 1.372 2.841 1.853 2.592 1.185 0.8532310065A10 ubiquitination Oasl2 Mm.228363 Hs.525059 0.57 0.481 0.239 0.3 0.298 0.556 0.889 0.485 0.49 0.503 0.444 1.286 1.008 0.781 0.712 0.665 0.788 0.711 0.418 2.706 5.92 1.438 0.4260610008D13 ubiquitination UBA52 Mm.43005 Hs.5308 3.941 3.603 1.87 2.233 2.392 3.99 0.813 1.048 8.161 3.99 8.214 2.039 4.797 3.536 4.752 4.94 7.141 5.417 9.54 3.735 3.435 1.763 1.4734930522D07 ubiquitination 4930522D07Rik Mm.55982 Hs.374027 1.181 0.855 0.607 0.344 1.117 1.097 1.462 0.762 1.478 1.558 1.091 1.177 1.336 1.086 1.391 1.031 1.197 0.904 1.401 1.18 1.45 0.278 0.9254931431F19 ubiquitination 4931431F19Rik Mm.158518 1.637 0.913 0.971 0.606 0.918 2.031 1.286 0.764 1.033 0.957 1.539 1.235 1.532 1.121 1.307 1.143 1.048 1.113 1.132 1.484 1.644 1.358 1.063110003A22 ubiquitination LOC137886 Mm.41643 Hs.155572 0.613 1.879 0.401 0.611 0.768 1.782 1.666 1.634 1.886 2.174 1.316 1.106 1.47 1.678 1.233 1.339 1.179 1.996 1.305 1.967 1.505 1.115 1.9922810407C17 ubiquitination NSFL1C Mm.272186 Hs.12865 0.698 1.51 1.068 0.496 0.9 1.727 1.127 1.006 1.16 0.674 0.792 1.144 1.407 1.311 0.949 1.307 1.243 0.945 0.477 1.238 1.48 0.969 1.4932610020P14 ubiquitination D8S2298E Mm.29301 Hs.153678 0.588 0.91 0.499 0.278 0.33 0.744 0.548 0.464 1.239 0.808 1.19 1.03 1.081 0.82 0.855 0.883 1.05 0.655 1.219 1.19 1.518 0.894 0.3794930550B20 ubiquitination USP45 Mm.154306 Hs.512802 2.344 2.409 1.134 0.918 1 2.755 1.634 1.189 3.074 2.666 5.117 1.757 3.2 1.298 2.534 1.442 2.334 2.414 3.928 3.499 3.544 1.871 0.8362610005K12 ubiquitination USP14 Mm.182319 Hs.75981 0.645 1.01 0.824 0.38 1.016 1.483 1.476 0.79 1.101 1.579 1.014 1.368 1.235 0.931 1.958 1.01 1.117 1.065 1.478 1.619 2.014 1.107 1.3774921514G19 ubiquitination USP15 Mm.244209 Hs.339425 0.877 0.849 0.914 0.336 1.098 2.128 1.993 1.115 1.028 0.849 1.375 1.115 1.059 0.883 1.329 1.001 1.127 1.44 1.522 1.39 1.506 1.612 1.0011200004E02 ubiquitination USP16 Mm.152941 Hs.99819 0.805 0.984 0.778 0.487 0.376 1.387 0.403 0.71 0.789 0.828 0.881 1.169 0.998 0.935 0.746 1.055 0.965 1.114 0.247 1.884 1.601 1.96 1.1699130006G10 ubiquitination USP39 Mm.281900 Hs.12820 0.748 0.824 0.412 0.815 0.529 1.163 1.08 0.907 1.303 2.729 2.546 2.134 1.603 1.857 3.393 2.299 2.674 2.575 2.185 1.642 1.27 0.561 0.3552600002H24 ubiquitination USP21 Mm.287370 Hs.8015 1.315 1.698 1.11 1.683 2.133 1.156 1.233 0.954 1.693 2.642 4.191 2.731 2.462 1.767 3.261 1.672 2.315 1.9 1.499 1.539 2.729 0.754 0.5011700124H18 ubiquitination Ube2l3 Mm.3074 Hs.446584 0.76 0.705 0.441 0.779 0.737 0.481 0.975 1.197 0.41 1.093 0.744 1.204 0.882 0.919 0.738 0.949 1.211 1.026 0.408 1.241 1.23 0.667 0.5520710008M05 ubiquitination UBE2J1 Mm.32920 Hs.184325 0.816 1.269 1.666 1.569 2.323 0.992 1.614 1.643 1.361 1.771 1.555 1.852 1.538 1.53 2.777 1.774 1.497 1.368 0.837 1.715 2.567 1.071 0.7291600023F01 ubiquitination FLJ13855 Mm.38802 Hs.369120 1.654 1.369 0.626 1.462 3.809 1.091 1.877 1.391 3.359 3.628 3.478 4.108 3.264 2.803 2.541 2.05 2.033 3.193 2.301 2.223 2.34 1.693 1.3992510040H03 ubiquitination UBE2M Mm.295670 Hs.406068 1.678 1.553 2.731 0.853 1.734 0.57 0.936 1.502 1.613 0.917 0.872 0.977 0.822 1.201 0.771 1.119 1.017 0.968 1.61 0.926 1.666 1.754 1.9082610009I04 ubiquitination UBE2B Mm.280233 Hs.385986 0.768 0.932 1.902 0.676 0.651 1.149 1.25 1.646 1.381 0.816 1.736 1.222 1.174 1.326 0.617 1.142 1.151 0.789 1.289 1.344 1.346 0.501 1.8362700059C12 ubiquitination UBE2G1 Mm.18485 Hs.78563 0.762 0.832 0.282 0.691 0.411 1.133 2.496 2.044 1.506 0.921 1.391 1.348 0.985 1.476 0.658 1.361 0.926 1.389 0.935 1.188 0.529 0.951 5.0562700084L22 ubiquitination HSPC150 Mm.284587 Hs.5199 0.503 1.067 0.737 0.574 0.504 0.924 0.411 1.223 0.396 0.719 0.467 1.047 1.09 1.406 0.614 1.301 1.548 0.898 1.313 1.284 0.788 2.26 0.4282810489I21 ubiquitination UBE2L6 Mm.38261 Hs.425777 0.685 1.072 1.214 0.645 0.724 0.738 0.791 0.947 0.414 1.198 0.581 1.259 1.064 1.014 0.742 1.108 1.152 1.014 0.686 1.286 1.614 1.178 0.2241700013N18 ubiquitination UBE2D2 Mm.45616 Hs.108332 0.969 0.852 1.18 0.778 1.569 1.055 1.265 1.458 0.749 1.14 2.574 1.47 1.158 1.11 0.587 1.186 1.476 1.089 0.795 1.786 2.5 1.31 0.1592510010F15 ubiquitination NCE2 Mm.183368 Hs.157804 0.669 1.098 1.386 0.878 2.1 0.945 1.309 0.99 1.257 1.294 0.657 1.31 1.182 1.229 0.798 1.119 1.323 0.945 1.207 1.398 2.054 1.653 0.4016130401J04 ubiquitination 6130401J04Rik Mm.122430 1.273 1.333 2.202 0.963 1.604 1.16 1.319 0.283 0.753 2.323 0.541 1.42 1.378 1.573 0.669 1.261 1.363 1.51 1.167 1.712 2.46 1.331 0.816720465F12 ubiquitination RPL28 Mm.3111 Hs.356371 1.151 1.608 0.508 1.421 2.118 1.781 1.201 1.467 1.063 1.219 1.062 1.872 1.907 1.302 0.775 1.333 1.65 1.116 1.237 1.864 2.139 1.041 1.6511200007B18 ubiquitination UBE2J2 Mm.295719 Hs.441183 0.596 1.062 1.178 0.508 0.446 0.589 1.397 1.529 1.199 0.942 0.911 1.235 1.056 1.424 0.945 1.345 1.15 1.221 1.522 1.247 1.031 1.69 2.4391810012G14 ubiquitination UBE2E3 Mm.1485 Hs.449501 1.048 1.173 1.456 1.073 1.584 1.039 1.743 1.356 1.787 2.921 3.023 2.343 1.651 1.743 6.838 1.884 2.289 2.554 1.884 2.631 2.781 0.862 0.2711110015A16 ubiquitination UBE2C Mm.89830 Hs.93002 1.131 1.67 1.608 1.642 2.033 1.717 0.917 1.007 0.516 0.623 1.034 1.842 1.322 1.808 1.299 1.341 1.484 1.165 0.586 1.499 1.574 1.176 0.3580910001J09 ubiquitination E2-EPF Mm.22491 Hs.462306 1.307 0.996 0.551 1.293 1.636 1.946 0.507 0.623 0.667 0.661 1.046 1.833 1.267 0.802 0.89 1.016 1.196 1.08 0.233 1.933 2.411 1.172 0.2351500026J17 ubiquitination UBE2N Mm.30233 Hs.458359 0.979 1.087 1.077 0.997 1.644 1.525 0.773 1.357 0.59 0.917 0.604 1.027 1.132 0.99 0.721 1.153 1.564 0.827 0.887 1.33 1.756 1.035 0.2181300019E17 ubiquitination UBE2I Mm.240044 Hs.302903 1.14 1.299 1.416 1.038 2.625 0.967 1.821 1.442 1.37 1.937 1.624 1.353 1.136 1.276 0.677 1.375 1.327 1.097 1.112 1.693 1.95 1.545 0.5751200003M11 ubiquitination UBE2R2 Mm.258805 Hs.11184 1.408 1.336 1.421 1.158 2.209 1.213 0.794 0.977 1.321 1.325 1.504 1.259 1.336 0.84 0.768 1.106 1.201 0.888 0.415 2.103 2.135 1.592 0.5133010034A12 ubiquitination FBX30 Mm.220327 Hs.321687 1.785 1.763 1.857 1.502 2.639 1.671 1.759 1.429 2.952 3.945 4.09 2.436 3.029 2.236 4.284 2.527 2.85 3.93 2.583 3.153 2.557 1.541 0.7512810025M06 ubiquitination FBXL12 Mm.24608 Hs.12439 2.544 2.624 1.696 1.816 0.812 0.543 1.064 0.79 4.403 4.509 3.596 3.672 3.274 1.362 1.557 1.807 2.224 2.486 2.124 2.47 2.301 1.525 0.799

Page 20: New High-Throughput Mapping of a Dynamic Signaling Network in … · 2005. 3. 11. · Science Supporting Online Material Barios-Rodiles, p. 1 Science Supporting Online Material High-Throughput

2610511F20 ubiquitination MGC15482 Mm.218350 Hs.194498 0.763 1.073 1.773 0.916 1.523 2.162 1.38 1.879 0.885 2.048 1.701 1.181 1.053 1.694 2.819 1.284 1.671 1.319 0.314 1.104 1.361 1.335 0.1531700026A16 ubiquitination FBXO30 Mm.276229 Hs.421095 1.429 1.447 1.806 1.904 4.784 2.812 1.259 1.357 1.17 2.55 2.19 3.14 2.253 1.703 3.766 1.542 1.93 2.528 2.475 2.054 3.181 0.98 1.6541200002G09 ubiquitination FBXO3 Mm.143768 Hs.406787 3.336 1.883 1.761 3.38 2.112 1.248 1.257 1.571 1.946 3.185 3.477 4.591 3.218 1.453 2.664 1.42 3.991 5.12 3.303 4.428 7.112 0.768 0.1435830426G16 ubiquitination FBXO34 Mm.11935 Hs.15467 1.332 1.54 1.272 1.612 3.021 1.286 1.008 1.186 2.482 2.925 4.908 2.373 2.102 2.162 2.13 2.138 2.212 2.22 2.657 2.663 2.654 0.857 0.084933422D21 ubiquitination FBXO24 Mm.158603 Hs.283764 2.579 1.82 1.77 2.114 1.72 1.03 1.396 0.999 2.744 2.89 4.273 4.088 2.948 2.015 2.107 2.237 2.878 3.439 2.183 4.113 4.046 1.046 0.1146430603C09 ubiquitination Skp1a Mm.42944 Hs.488433 1.184 1.671 1.793 1.835 2.208 0.788 1.473 0.998 0.907 1.253 1.528 2.483 1.653 1.235 1.006 0.953 1.667 1.142 1.202 2.035 1.595 0.893 0.3094932411N15 ubiquitination CUL2 Mm.291707 Hs.82919 1.082 1.19 0.644 1.518 1.607 0.872 0.943 0.439 1.744 1.784 2.11 2.485 1.575 1.96 2.628 1.573 2.275 1.809 1.334 2.24 2.988 0.81 0.2328430423K24 ubiquitination CUL5 Mm.218910 Hs.440320 1.24 0.986 0.354 1.187 2.363 1.438 0.895 0.866 1.578 2.153 3.495 2.271 1.586 1.407 2.103 1.503 1.564 1.705 0.773 1.616 3.482 1.374 0.1582700050M05 ubiquitination CUL4B Mm.26885 Hs.155976 0.875 1.415 1.302 1.124 2.855 1.768 1.64 1.347 0.597 0.973 1.047 1.209 0.956 1.879 1.766 1.331 1.848 1.911 1.512 1.444 1.252 0.581 0.093NM_003900 ubiquitination SQSTM1 Mm.40828 Hs.182248 3.233 4.155 2.828 3.528 3.314 2.244 2.209 2.051 3.547 2.097 2.502 5.621 5.214 3.519 4.264 3.782 4.461 5.016 4.714 6.517 7.809 1.397 0.8681110001N06 WD40 FLJ11294-v1 Mm.277705 Hs.107000 0.882 0.726 0.36 0.567 0.92 1.243 0.677 1.148 2.078 2.742 4.609 1.305 1.111 1.257 1.226 1.573 1.017 1.395 1.44 1.23 1.072 1.036 2.1571200006M05 WD40 PC326 Mm.219421 Hs.280168 3.757 1.793 2.455 1.434 1.456 2.256 0.921 1.097 4.522 5.653 6.417 2.576 2.512 2.509 3.455 2.269 3.955 4.054 4.144 2.974 2.708 0.944 0.6811300004C11 WD40 GTF3C2 Mm.271923 Hs.75782 2.009 1.228 1.77 0.695 1.068 1.992 0.993 1.117 1.672 1.728 1.854 1.462 1.571 1.5 1.243 1.991 1.241 1.875 1.271 1.656 2.162 0.71 0.8491300017E19 WD40 PPP2R2D Mm.258739 Hs.380372 4.658 4.67 4.19 5.944 1.637 1.798 0.78 1.173 2.491 1.734 2.124 2.342 2.35 1.562 1.475 2.074 1.544 1.689 2.493 2.921 4.511 1.109 0.7611500001L20 WD40 KIAA1892 Mm.28891 Hs.102669 1.911 1.312 1.54 0.684 0.887 2.549 1.063 0.376 4.127 8.963 5.381 1.54 1.473 1.679 2.627 2.841 2.672 3.824 3.398 1.092 1.5 0.502 0.8461500009K01 WD40 APG16L Mm.272972 Hs.419213 1.031 0.839 0.527 0.208 0.818 1.637 1.092 0.964 2.483 3.774 3.066 1.074 1.05 1.341 1.768 2.15 1.52 1.977 3.083 0.976 0.879 0.373 1.0041600015H11 WD40 PRPF4 Mm.22833 Hs.374973 1.437 1.483 0.793 0.63 0.904 1.167 1.5 1.15 2.341 3.214 3.525 1.419 1.49 1.546 1.292 1.998 1.554 2.33 2.456 1.839 1.582 0.568 0.8251700012F10 WD40 HAN11 Mm.9671 Hs.410596 2.562 2.056 1.917 1.046 1.185 1.061 1.395 1.271 1.442 2.404 2.092 1.045 2.227 1.666 1.25 1.301 3.194 2.676 1.882 2.678 2.123 1.118 0.7561700057K18 WD40 CSTF1 Mm.26944 Hs.172865 1.249 1.436 1.039 0.864 0.678 1.35 0.607 0.81 0.866 0.724 0.84 0.836 0.937 1.114 0.517 0.817 0.951 0.627 0.358 1.208 1.134 0.632 0.851700120F24 WD40 WDFY1 Mm.293273 Hs.44743 1.837 2.731 1.086 0.378 1.382 1.354 0.821 0.704 1.144 1.142 0.927 1.848 1.736 1.268 1.018 1.218 1.121 1.241 0.926 1.294 1.741 1.161 0.972310011G05 WD40 FLJ11294-v2 Mm.277705 Hs.107000 1.219 1.016 0.696 0.603 0.642 0.982 0.661 0.677 3.297 5.593 3.75 1.039 1.306 1.655 1.931 2.021 1.461 2.136 1.596 1.369 1.685 0.732 0.9662310012I10 WD40 WDR18 Mm.35828 Hs.325321 1.067 1.245 1.541 0.554 1.049 1.25 0.684 0.473 1.648 2.187 1.443 1.235 1.229 1.711 1.88 1.922 1.474 1.856 1.658 1.91 1.08 0.403 0.7452310042N09 WD40 CDC20 Mm.289747 Hs.82906 1.619 1.987 1.443 0.781 0.823 1.448 0.638 0.755 2.595 3.362 3.664 1.591 1.863 1.229 1.343 1.766 1.839 1.914 2.122 1.608 1.653 0.451 0.7722410003J24 WD40 KATNB1 Mm.28382 Hs.275675 1.529 1.489 1.492 0.588 0.722 1.295 0.439 0.884 2.039 3.644 2.953 1.868 2.165 1.798 2.427 2.09 1.57 1.783 2.255 1.786 1.621 0.6 0.5992410003L22 WD40 Nup37 Mm.222184 Hs.5152 1.536 1.071 1.515 0.559 1.003 1.202 0.948 1.097 2.308 3.214 3.996 1.864 1.767 1.816 1.83 1.645 1.985 1.981 1.679 1.441 1.15 0.491 0.832410022P04 WD40 CKN1 Mm.212208 Hs.32967 1.111 0.949 0.83 0.451 0.804 1.159 0.759 0.561 1.042 1.068 1.225 0.914 1.166 1.023 0.73 1.007 1.168 0.929 0.89 0.941 1.151 0.403 0.8120610007C05 WD40 ARPC1B Mm.30010 Hs.433506 2.288 2.129 1.35 1.015 0.954 1.592 0.495 0.605 1.05 1.234 1.102 1.364 1.365 1.048 0.743 0.901 1.12 0.928 1.046 2.362 2.557 0.521 0.6754833431H09 WD40 GNB3 Mm.130145 Hs.71642 2.191 1.803 1.415 0.723 1.131 1.573 0.781 0.489 3.293 3.145 3.653 2.163 1.626 1.566 1.983 1.737 2.449 1.999 2.14 1.754 1.56 0.74 0.6672510003I12 WD40 TBL2 Mm.36746 Hs.52515 0.557 0.988 0.747 0.497 0.452 0.418 0.299 0.22 1.504 1.28 1.335 1.107 1.093 1.123 1.167 1.234 1.401 1.382 1.611 3.685 2.915 0.371 0.2014930447M07 WD40 CIAO1 Mm.45179 Hs.12109 1.208 1.183 0.833 0.6 0.778 0.735 0.931 0.755 0.996 1.339 0.555 1.285 1.371 1.118 0.726 1.343 0.908 0.757 0.566 1.612 1.818 0.698 0.732700045C12 WD40 EIF3S2 Mm.250874 Hs.192023 1.577 1.241 0.947 0.417 0.871 1.11 0.46 0.915 1.152 2.035 1.208 1.587 1.309 1.136 1.205 1.376 1.336 1.46 2.168 1.144 0.741 0.383 0.6571110003H02 WD40 SEC13L1 Mm.29296 Hs.227949 0.991 0.987 1.681 0.338 1.186 1.399 1.363 0.256 1.085 1.204 0.98 1.001 1.115 1.105 0.842 1.257 0.964 0.887 1.045 1.378 1.457 0.674 0.8994933427G20 WD40 Gnb1l Mm.236139 1.061 1.101 0.479 0.373 0.514 0.788 0.772 0.856 1.796 2.385 2.77 0.939 1.054 1.168 0.926 0.872 1.404 1.313 0.913 1.54 1.151 0.621 0.7264921538B03 WD40 WDR20 Mm.219475 Hs.55209 1.88 1.656 0.875 0.824 0.985 1.96 0.357 0.576 1.605 2.524 2.297 1.963 2.663 1.18 1.144 0.937 1.802 1.654 1.71 1.778 1.689 0.777 0.6652600017H24 WD40 CHAF1B Mm.274222 Hs.75238 2.272 1.663 1.33 0.855 0.654 0.987 0.422 0.647 1.034 1.079 1.354 1.866 1.661 0.995 1.054 0.858 1.348 1.078 1.508 1.998 1.909 0.799 0.4562700038M07 WD40 WSB1 Mm.287354 Hs.315379 2.274 1.298 1.89 1.115 1.243 1.712 1.046 1.059 3.782 4.44 4.267 3.082 2.793 1.911 2.396 2.161 1.442 2.444 1.997 2.215 2.319 1.222 0.920610009C03 WD40 HPRP8BP Mm.29606 Hs.379357 0.833 0.999 0.964 0.461 0.476 0.766 0.571 0.571 0.776 1.196 0.771 0.895 0.654 0.964 0.622 0.97 1.035 1.23 0.992 1.624 1.068 0.12 0.9162610044M17 WD40 WDR8 Mm.46508 Hs.31714 2.178 2.921 1.048 0.839 0.695 1.694 0.373 0.399 1.201 1.189 1.026 1.529 1.62 0.905 0.721 1.207 0.901 0.891 0.963 2.202 2.039 0.646 0.5573230401I12 WD40 RAE1 Mm.4113 Hs.371698 2.392 1.661 1.345 0.644 0.842 1.472 0.275 0.891 1.251 2.065 1.318 1.361 1.518 1.179 0.859 1.47 0.942 1.264 1.259 1.529 1.339 0.687 1.4512810452E04 WD40 PREB Mm.15928 Hs.279784 1.792 2.361 1.794 0.916 1.011 1.442 0.986 0.676 3.852 5.939 4.612 3.148 3.105 2.173 2.305 2.276 2.441 2.48 2.845 2.247 2.226 0.545 0.8435730411P10 WD40 WDR13 Mm.284162 Hs.12142 1.636 1.991 1.497 0.672 0.561 0.583 0.591 0.506 2.821 3.284 3.453 1.459 1.762 1.775 1.98 1.491 2.048 1.888 2.014 1.796 1.511 0.609 0.5561200003H23 WD40 CDC40 Mm.46063 Hs.116674 2.849 3.644 2.273 2.607 1.385 1.736 1.46 1.953 1.044 1.309 1.196 1.39 1.749 1.67 1.274 1.002 1.788 1.435 2.076 16.4 15.95 0.69 0.8762700038L12 WD40 REC14 Mm.245683 Hs.125457 2.558 1.372 1.418 1.168 2.081 2.374 0.982 1.439 2.331 3.224 2.924 2.373 2.2 1.864 3.277 1.469 2.143 2.482 2.535 3.33 3.232 0.805 0.6530610012H09 WD40 GNB2 Mm.30141 Hs.185172 1.97 1.913 1.428 0.969 0.9 1.257 0.929 0.678 3.408 3.071 3.571 2.208 1.958 1.3 1.846 1.527 1.641 1.64 2.37 2.23 2.003 0.617 0.5962610203K23 WD40 SMU-1 Mm.289929 Hs.327749 1.156 0.897 0.947 0.383 0.903 1.421 0.612 0.918 0.777 1.029 0.702 0.912 0.919 1.111 0.702 1.196 1.142 1.215 1.18 2.032 1.365 0.796 0.5644930535L09 WD40 PLRG1 Mm.286349 Hs.249996 1.74 1.627 1.368 0.666 0.876 1.248 0.673 0.971 1.385 1.808 1.888 1.445 1.353 1.173 0.985 1.65 1.289 1.743 2.152 2.423 2.186 0.782 0.6776330404L05 WD40 PPP2R2B-v1 Mm.259912 Hs.380764 2.324 1.942 2.007 0.794 1.696 1.505 1.061 0.98 2.89 3.767 3.362 2.185 2.374 2.291 1.864 2.187 1.942 2.359 2.368 2.809 2.457 0.652 0.9082510005J23 WD40 PEX7 Mm.2440 Hs.79993 1.18 1.216 0.701 0.641 0.895 1.033 0.57 1.105 0.77 0.817 0.664 1.174 1.019 1.005 0.554 0.922 1.381 0.873 0.996 1.267 1.088 0.686 0.6762410080P20 WD40 FLJ20195 Mm.271719 Hs.286261 0.327 0.461 0.406 0.266 0.169 0.192 0.189 0.215 0.329 0.378 0.294 0.678 0.631 0.859 0.377 0.649 0.741 0.526 0.517 0.499 0.559 0.176 0.2712610024M05 WD40 RBBP4 Mm.12145 Hs.16003 1.415 0.902 0.941 0.568 0.808 0.975 0.627 0.29 0.898 1.324 0.847 1.274 1.185 1.152 0.943 1.203 1.051 1.103 1.071 2.332 1.825 1.153 0.8312410026A21 WD40 NEDD1 Mm.2998 Hs.14456 1.374 1.164 1.326 0.694 1.421 2.859 0.676 1.053 1.457 1.223 1.489 1.148 1.117 1.473 0.99 1.764 1.176 1.185 0.623 1.657 1.364 0.66 0.762510040D07 WD40 DKFZP434C245 Mm.23054 Hs.59461 0.866 1.322 0.961 0.622 0.852 1.254 0.947 0.851 1.699 1.827 1.776 1.328 1.08 1.268 0.82 1.397 1.049 1.096 0.696 1.652 1.389 0.542 0.5615730515M10 WD40 GNB2L1 Mm.5305 Hs.5662 0.995 1.293 1.24 0.461 0.857 1.196 0.67 0.643 1.151 1.267 1.298 1.332 1.376 1.214 0.966 1.16 0.857 0.919 1.327 1.541 0.957 0.454 0.6155930415H02 WD40 PAK1IP1 Mm.24789 Hs.310231 0.884 1.303 2.012 0.685 1.481 1.35 0.902 0.944 0.736 1.357 0.672 1.076 1.363 1.477 0.798 1.037 1.172 1.145 1.447 3.182 3.103 1.22 0.9512610205J09 WD40 PWP1 Mm.18834 Hs.172589 1.728 1.456 0.814 0.776 1.238 1.522 1.41 0.874 1.522 1.915 1.572 1.769 1.803 1.957 1.638 1.69 2.167 2.971 2.54 3.823 3.33 0.641 0.5782810410J09 WD40 RNU3IP2 Mm.239997 Hs.153768 1.438 1.515 1.21 0.604 0.778 0.91 0.536 0.639 0.79 2.118 1.06 0.994 1.123 1.302 0.726 1.547 1.267 1.797 1.382 11.35 7.331 0.901 0.4882900026H06 WD40 PPP2R2B-v2 Mm.259912 Hs.380764 4.175 3.285 2.227 3.806 2.292 2.971 0.934 0.87 2.357 1.903 3.046 1.782 1.969 1.746 1.603 2.155 1.314 1.778 1.833 2.514 3.351 0.34 0.9454930533L09 WD40 FBXW5 Mm.273981 Hs.82023 2.816 2.289 2.465 0.93 1.688 2.458 1.252 1.035 2.554 3.919 3.11 2.556 3.282 1.943 1.724 2.113 2.455 2.363 4.243 1.592 1.772 0.646 0.663NM_011499 WD40 UNRIP Mm.22584 Hs.3727 1.94 0.98 1.528 1.032 1.966 0.989 0.837 1.065 0.502 1.114 0.822 1.513 1.254 0.96 0.932 1.029 1.208 1.066 1.056 2.229 3.185 0.532 0.0790610043C19 kinase CSNK2A2 Mm.51136 Hs.82201 1.391 1.718 0.777 0.827 2.2 1.11 0.85 0.871 5.509 3.346 4.439 1.093 1.447 1.114 1.36 1.803 1.439 2.131 1.632 6.162 3.999 1.824 0.5154932415A06 kinase DKFZp434E1822 Mm.159174 Hs.255960 1.18 1.134 0.698 1.01 1.524 1.137 1.123 1.042 1.744 2.752 1.349 1.513 1.804 1.027 1.346 1.564 1.896 1.959 2.002 3.674 3.37 1.833 0.4474933411O17 kinase CDKL1 Mm.132325 Hs.380788 1.996 2.296 1.475 1.538 2.137 0.703 1.444 1.803 1.456 3.341 1.494 1.463 1.394 1.916 1.283 1.988 1.606 1.886 1.156 3.197 3.025 0.858 0.4354933424F08 kinase C14orf20 Mm.171300 Hs.314432 0.841 1.12 0.546 1.064 0.654 0.394 0.387 0.422 2.138 4.492 2.457 1.646 1.385 0.887 1.511 0.835 1.385 1.524 2.098 2.054 2.488 3.605 0.531300007C09 kinase NEK6 Mm.143818 Hs.387222 1.422 2.708 0.895 1.756 3.179 1.656 0.615 0.723 2.026 3.886 2.936 2.283 1.995 1.222 2.212 1.039 1.313 1.659 0.823 2.171 2.641 3.593 0.5061300013P10 kinase PCTK3 Mm.28130 Hs.445402 1.744 2.733 0.936 1.479 1.469 0.796 0.378 0.382 1.238 2.716 1.678 1.201 1.338 0.907 1.423 1.027 1.204 1.284 0.833 1.683 2.344 1.096 0.3381700054C12 kinase STK35 Mm.260334 Hs.100057 1.758 2.421 0.794 1.724 3.209 1.522 1.522 1.751 2.618 4.157 1.561 1.411 2.268 1.615 2.622 1.982 2.487 3.185 2.484 2.852 3.591 1.851 0.5421700091F14 kinase 1700091F14Rik Mm.159026 2.675 2.668 1.088 1.41 1.913 0.898 0.611 0.58 3.383 4.114 2.993 1.521 2.936 1.27 2.047 1.746 1.79 1.931 1.779 2.396 3.11 1.19 0.3822010016G11 kinase MKNK2 Mm.42126 Hs.512094 1.343 1.158 1.03 0.682 2.293 0.807 1.274 1.1 8.012 9.776 7.753 1.175 1.298 2.069 2.125 2.155 4.386 4.515 3.229 1.462 1.861 1.153 0.5782210420D18 kinase RIPK2 Mm.112765 Hs.103755 1.633 2.257 0.624 0.639 4.681 1.901 1.29 1.344 1.489 1.553 1.465 1.091 1.058 2.049 0.741 2.407 1.273 1.092 1.17 2.431 3.702 1.366 0.8372410015K02 kinase MELK Mm.268668 Hs.184339 1.81 1.922 0.463 0.921 1.801 1.157 0.992 1.311 0.86 1.319 1.034 1.228 1.187 1.537 1.11 1.816 1.343 1.413 0.95 2.675 2.059 1.533 0.8062410042H09 kinase AURKB Mm.3488 Hs.442658 1.699 2.609 0.611 1.408 1.532 0.759 0.761 0.791 2.517 5.639 2.879 2.676 2.164 1.865 2.054 1.539 2.423 2.401 2.507 1.978 1.674 1.911 0.3212410048M24 kinase MKNK1 Mm.209327 Hs.79516 1.219 1.412 0.951 1.078 1.73 1.051 0.369 0.613 0.866 2.031 1.112 1.689 1.545 1.083 0.837 0.819 0.704 0.931 0.84 2.378 1.822 2.021 0.3922510027C03 kinase MAP2K3 Mm.18494 Hs.180533 3.454 8.472 2.783 7.691 19.24 4.675 1.727 1.243 2.116 3.744 3.066 3.748 3.534 1.823 2.779 1.909 3.423 2.62 0.971 2.679 3.286 1.64 0.5022600014H12 kinase WEE1 Mm.287173 Hs.249441 2.19 2.47 1.656 3.448 1.403 1.485 0.836 0.506 0.695 1.707 0.443 1.392 1.85 1.259 1.282 1.596 1.337 1.943 1.863 2.162 3.146 2.939 0.5142610001I03 kinase CHEK1 Mm.16753 Hs.24529 1.868 1.924 0.828 1.168 3.222 1.523 0.701 0.922 1.163 2.306 0.723 1.108 1.496 1.469 0.967 1.504 1.025 1.389 1.417 2.829 2.627 1.805 0.5472610009E10 kinase IKBKB Mm.277886 Hs.413513 1.854 1.561 0.764 0.918 2.155 1.365 1.197 1.394 2.098 3.878 2.35 1.448 1.974 2.333 3.01 3.035 2.792 2.513 2.186 2.406 2.605 1.298 0.393

Page 21: New High-Throughput Mapping of a Dynamic Signaling Network in … · 2005. 3. 11. · Science Supporting Online Material Barios-Rodiles, p. 1 Science Supporting Online Material High-Throughput

2610019A05 kinase LYK5 Mm.37985 Hs.279731 1.154 1.14 0.821 0.753 3.146 1.375 1.16 0.847 1.097 1.507 1.365 1.306 1.217 1.318 0.838 1.502 0.837 1.112 0.404 1.429 1.87 1.066 0.5312610203O19 kinase CDK4 Mm.6839 Hs.95577 1.733 1.862 0.837 0.895 1.81 1.084 1.218 1.237 1.737 6.429 1.423 1.326 1.393 1.996 1.922 1.882 2.052 2.301 3.039 1.664 1.687 1.375 0.6354933428O03 kinase EIF2AK4 Mm.26931 Hs.412102 2.276 2.427 1.486 1.832 3.358 1.535 1.354 0.934 2.513 5.824 2.664 4.192 4.226 1.319 2.447 1.252 2.01 2.526 2.947 2.967 2.954 2.037 0.4721110062I02 kinase DAPK2 Mm.41755 Hs.129208 1.419 2.867 0.889 1.714 2.021 1.159 0.859 0.551 3.628 3.688 3.359 1.882 2.475 1.297 1.641 1.192 1.606 1.773 1.029 1.913 1.959 2.646 0.3951200006A05 kinase CSNK1D Mm.216227 Hs.378918 1.817 1.786 0.774 1.339 2.474 0.972 0.573 0.561 2.73 3.215 1.504 1.328 1.447 0.96 1.617 1.172 1.628 2.125 0.97 2.786 2.344 1.451 0.3051200013B22 kinase SNARK Mm.100666 Hs.172012 3.831 4.619 1.436 2.56 3.68 1.744 1.036 0.863 2.553 5.875 3.242 1.543 2.424 2.501 3.016 2.466 1.79 2.533 1.214 2.71 2.592 1.649 0.3951700014N07 kinase STK22C Mm.143802 Hs.512763 2.458 2.329 1.317 1.655 5.237 1.52 1.24 0.894 2.056 2.836 2.645 1.513 1.972 1.632 1.522 2.491 1.78 2.001 1.372 2.041 2.946 1.641 1.651700029P02 kinase STK22D Mm.18470 Hs.333138 2.043 2.335 1.239 1.545 2.23 1.513 0.571 0.51 2.872 5.552 2.555 1.521 2.279 1.34 2.103 1.755 2.453 2.471 2.521 2 2.927 0.947 0.3162810003O05 kinase FANCL Mm.18875 Hs.411433 1.275 2.026 0.88 1.139 2.221 0.729 0.757 0.943 5.917 8.788 5.395 1.444 1.681 1.697 3.656 1.814 3.812 2.854 2.803 2.65 2.521 1.621 0.4432810434B10 kinase TOPK Mm.24337 Hs.104741 0.998 1.391 0.988 0.817 3.007 1.242 2.221 0.37 0.846 1.58 1.017 1.584 1.382 1.075 0.838 0.981 0.988 1.31 1.169 1.548 1.348 1.857 0.7032810454O04 kinase KIS Mm.209150 Hs.127310 3.886 4.071 0.954 2.238 3.889 2.221 1.484 1.552 3.298 7.219 2.313 2.526 3.842 1.498 3.491 1.742 2.48 2.39 3.418 4.081 4.911 0.902 0.4262210022N24 kinase OSR1 Mm.293565 Hs.95220 2.228 1.759 1.407 1.739 2.989 1.487 0.841 0.874 2.569 5.118 2.762 1.812 2.707 1.304 2.966 2.448 3.475 3.399 2.419 3.459 3.455 1.614 0.3792810011D23 kinase CAMK2D Mm.255822 Hs.111460 1.567 1.827 0.811 0.744 5.146 1.355 1.329 1.536 0.82 1.821 1.447 1.026 1.16 1.277 0.979 1.547 0.917 1.154 1.277 2.085 1.845 1.782 0.6354632401F23 kinase NEK8 Mm.23788 Hs.448468 2.204 1.832 1.098 1.26 2.38 0.932 0.405 0.738 3.098 5.094 3.219 1.909 2.598 2.306 4.24 2.546 2.707 2.255 2.452 2.38 2.678 0.6 0.4354632404G05 kinase CSNK1A1 Mm.26908 Hs.318381 1.839 1.443 0.777 0.884 2.749 1.137 1.65 1.477 2.943 7.335 1.91 1.226 1.527 1.558 1.714 2.204 1.269 1.278 1.528 1.447 2.154 0.912 0.5934833426L05 kinase HRI Mm.220921 Hs.434986 1.239 1.219 0.621 0.809 1.636 1.56 0.951 1.156 2.689 4.656 2.634 1.279 1.294 1.384 2.102 1.957 1.362 1.474 1.221 1.882 1.786 1.82 0.8264921505G21 kinase STK33 Mm.79075 Hs.148135 0.624 1.4 1.15 0.848 1.844 1.203 1.162 1.348 0.438 1.783 0.578 1.58 1.231 1.176 0.922 0.936 0.875 1.13 1.013 1.886 1.489 1.927 0.6964921506N09 kinase TLK2 Mm.126976 Hs.445078 0.874 1.306 1.373 1.011 2.529 1.91 1.022 1.064 1.767 2.877 2.089 1.674 1.49 1.261 0.83 1.103 1.479 1.463 0.763 1.673 1.934 1.112 0.4534930444A02 kinase FLJ23356 Mm.17631 Hs.277431 0.826 1.082 0.722 0.685 1.587 0.845 0.525 0.44 12.6 11.57 10.71 1.197 1.37 1.356 1.684 1.413 10.46 3.598 8.571 1.634 1.396 0.807 0.094930588P12 kinase PFTK1 Mm.6456 Hs.57856 2.106 2.162 1.145 1.523 2.309 1.241 1.31 1.243 3.786 8.327 3.718 1.318 1.677 2.366 3.583 2.311 2.479 3.118 1.821 2.623 3.181 1.739 0.5114930594I21 kinase STK22C Mm.143802 Hs.512763 1.967 2.467 1.535 1.426 4.925 2.334 1.074 1.275 2.374 2.888 2.811 1.411 1.913 1.908 1.585 2.086 1.421 1.828 1.736 1.41 2.559 1.391 0.5455730422C08 kinase PAK1 Mm.260227 Hs.64056 2.337 3.303 1.243 1.714 3.307 2.498 0.98 1.417 10.84 12.07 9.409 1.67 3.344 1.627 5.078 2.986 2.933 3.221 4.234 5.722 5.818 1.083 0.3046330415L08 kinase IRAK2 Mm.152142 Hs.424542 2.278 3.725 1.019 1.599 1.647 1.425 0.286 0.375 1.418 1.381 1.091 1.26 1.754 0.982 1.075 1.159 0.868 0.791 0.588 4.491 5.537 0.774 0.1976430598J10 kinase PCTK2 Mm.45746 Hs.258536 1.006 1.44 0.802 1.116 1.19 0.764 1.243 0.429 1.682 4.816 1.64 1.177 1.183 1.286 1.645 1.647 1.137 1.661 0.719 1.923 2.234 1.498 0.5849030416P08 kinase MYO3A Mm.221230 Hs.148228 0.731 2.317 0.984 0.86 1.623 1.452 1.432 1.451 2.216 7.458 2.795 1.985 1.344 1.875 2.404 1.571 1.931 2.76 1.248 1.73 1.335 1.668 0.8019130411F08 kinase CHUK Mm.3996 Hs.198998 0.694 2.132 1.09 1.187 2.557 1.716 0.925 1.111 1.539 3.706 1.661 1.75 1.412 1.788 2.33 1.679 1.904 2.166 2.246 1.949 2.513 2.218 0.6789130423C03 kinase CDK6 Mm.88747 Hs.38481 1.061 1.053 0.694 0.64 1.404 0.768 0.467 0.545 1.821 4.204 1.145 1.248 1.32 0.887 1.373 1.064 1.475 1.564 1.829 0.903 1.406 0.774 0.2924432415E19 kinase MAP4K5 Mm.291936 Hs.246970 0.704 0.533 0.278 0.282 0.145 0.194 0.348 0.247 0.426 0.414 0.491 1.044 0.898 0.603 0.611 0.689 0.615 0.509 0.309 1.191 1.185 1.181 0.245L11695 kinase TGFBR1 Mm.197552 Hs.28005 1.764 1.688 1.31 1.431 2.518 0.492 1.035 0.865 231.1 61.05 102.2 1.473 1.373 14.18 11.6 11.6 45.91 58.17 41.19 2.881 2.356 0.773 0.089NM_001204 kinase BMPR2 Mm.7106 Hs.53250 1.229 0.947 0.808 1.175 1.842 0.883 1.494 0.574 19.09 3.712 13.4 1.237 1.302 1.538 1.003 1.427 1.11 1.588 16.44 2.288 2.66 0.693 0.338L29479 kinase STK18 Mm.3794 Hs.172052 1.351 1.571 2.311 1.4 3.463 1.753 1.31 0.873 3.217 1.845 1.65 1.635 1.67 1.446 1.439 1.779 1.645 2.164 1.68 2.576 2.176 0.721 0.186D76446 kinase MAP3K7 Mm.258589 Hs.290346 2.321 1.753 1.18 1.305 0.716 0.614 0.472 0.267 2.285 1.54 1.846 1.817 1.348 1.194 0.976 1.276 1.244 1.089 1.541 5.075 4.259 0.723 0.3341200014P03 TPR KNSL8 Mm.279599 Hs.53447 2.229 2.293 1.212 1.162 1.529 1.915 0.687 0.503 1.398 0.767 1.642 1.311 1.674 0.817 0.93 1.082 1.827 0.895 2.121 1.757 2.424 1.698 0.8184933404O19 TPR DKFZP434H0115 Mm.31590 Hs.201134 1.058 0.647 0.403 0.39 0.491 0.99 0.788 0.863 0.64 0.672 0.844 1.194 0.965 1.018 0.61 0.747 0.876 0.766 0.653 1.726 1.236 0.891 0.7374930506L13 TPR FLJ13946 Mm.282339 Hs.128384 1.472 1.188 0.332 0.524 1.057 1.55 1.013 1.732 1.721 1.573 1.562 0.998 1.164 2.457 2.195 2.253 1.911 1.536 1.038 1.369 1.149 1.619 0.6454930564J03 TPR PPID Mm.295252 Hs.143482 1.666 1.469 0.664 0.775 0.891 1.134 1.387 1.011 1.652 1.356 1.649 1.068 1.412 1.469 0.828 1.325 0.962 0.93 1.437 1.775 1.691 1.815 3.2530610033N24 TPR STUB1 Mm.45165 Hs.414390 2.543 2.092 0.571 0.851 0.909 1.786 0.417 0.302 3.811 3.18 9.038 1.618 4.725 1.137 2.327 1.191 2.124 2.634 3.269 1.973 3.168 1.266 0.7360610011H21 TPR EIF3S6IP Mm.206404 Hs.119503 1.271 0.721 0.4 0.486 0.42 0.661 0.519 0.485 1.689 1.368 1.761 1.119 1.143 0.602 1.645 0.924 1.022 0.722 1.1 1.768 2.296 1.562 0.4132810460C24 TPR FLJ20343 Mm.69739 Hs.171044 1.417 0.643 0.539 0.385 0.786 0.854 1.178 1.017 1.044 1.116 1.244 1.314 0.993 0.638 1.172 0.948 0.892 0.919 1.086 1.316 1.346 1.982 0.8694833412C19 TPR TTC1 Mm.271974 Hs.7733 1.54 0.695 0.679 0.352 1.015 1.21 1.143 0.617 2.821 7.114 3.41 1.227 1.144 0.955 2.394 1.078 1.064 1.125 1.546 1.415 1.524 1.412 1.484921531G14 TPR KIAA0103 Mm.244512 Hs.130456 0.997 0.602 0.524 0.231 0.709 1.487 1.08 0.545 0.717 0.987 0.779 1.097 0.783 0.737 0.836 0.833 0.933 0.812 0.848 1.609 1.527 1.498 1.0391700016J08 TPR PEX5R Mm.151332 Hs.46780 1.127 0.926 0.728 0.51 1.289 0.817 1.171 0.357 1.127 1.538 1.555 1.325 0.673 1.12 1.308 1.167 1.244 1.702 1.27 1.251 1.186 1.848 0.6171300003O07 TPR APPBP2 Mm.271997 Hs.84084 0.614 0.881 0.525 0.367 0.325 0.751 0.578 0.714 1.434 1.096 0.925 0.913 1.006 1.396 1.388 1.148 1.028 1.059 1.354 1.755 2.023 1.471 0.8092210019E14 TPR MGC29649 Mm.259531 Hs.31704 2.149 1.608 0.979 0.707 1.381 1.704 1.51 1.163 1.11 2.095 1.63 0.998 1.418 1.081 1.287 1.574 1.272 0.971 2.016 1.671 2.408 1.346 2.1012010003F24 TPR DNAJC7 Mm.258140 Hs.446481 1.116 1.012 0.498 0.48 0.313 1.006 0.387 0.239 1.471 2.021 2.1 1.087 1.667 0.871 1.33 0.832 1.207 0.909 1.235 1.006 3.467 0.695 0.3392900001O04 TPR OSRF Mm.254979 Hs.280811 1.774 1.102 1.019 1.012 1.11 1.293 1.15 0.612 0.995 1.156 0.761 1.454 1.612 0.844 1.574 0.863 0.971 0.804 1.008 2.212 2.832 2.31 0.5992410024H11 TPR CDC23 Mm.196638 Hs.153546 1.465 2.134 0.564 0.583 0.504 0.973 0.44 0.308 1.487 1.043 1.324 1.146 1.593 0.686 1.018 0.763 1.212 0.673 1.259 2.366 2.836 1.516 0.342510006G12 TPR ANAPC5 Mm.45312 Hs.7101 1.239 0.752 0.573 0.499 0.514 1.633 0.875 0.414 2.148 2.255 3.028 1.425 1.392 0.883 1.797 0.852 1.258 1.042 1.219 3.824 3.623 3.395 0.7062510042P03 TPR FLJ13946 Mm.275109 Hs.128384 0.882 0.589 0.645 0.315 0.761 1.223 1.31 1.039 1.279 1.747 1.977 1.118 0.896 1.103 1.2 1.044 0.973 0.806 0.905 1.288 1.728 1.353 0.652610009O10 TPR STIP1 Mm.258633 Hs.257827 2.276 1.728 1.084 0.914 1.211 1.422 0.871 1.83 2.562 1.226 1.342 0.951 1.438 1.948 0.998 1.486 1.267 1.277 0.596 1.605 1.905 1.323 1.7032610029G12 TPR AIP Mm.10433 Hs.412433 1.483 1.333 0.911 0.548 1.155 1.817 1.043 0.579 0.952 0.973 0.917 1.009 1.39 0.909 0.915 1.24 1.157 0.937 1.291 1.545 2.482 1.386 1.1439130020K17 TPR FLJ10890 Mm.248504 Hs.17283 2.397 1.243 1.297 1.037 0.976 1.563 1.124 0.79 2.47 1.55 2.467 1.458 2.732 1.222 3.367 1.447 1.647 1.471 3.697 4.541 6.878 1.844 1.0171300019C06 TPR FLJ22054 Mm.24425 Hs.13277 2.078 0.958 0.822 0.812 0.985 1.836 1.093 0.749 1.467 1.179 1.703 1.195 1.462 1.016 1.647 0.967 1.219 1.185 2.58 2.252 3.522 1.804 1.162310015L07 TPR 2310015L07Rik Mm.158287 Hs.207472 1.513 1.134 0.778 0.825 0.508 1.254 0.545 0.256 1.481 1.789 0.946 1.412 1.669 0.69 1.678 0.713 1.138 0.989 0.689 2.468 2.867 1.745 0.6092310042P20 TPR FLJ21908 Mm.12255 Hs.323473 1.21 0.69 0.461 0.348 1.011 1.582 0.66 0.379 0.583 3.686 1.107 1.145 1.057 0.717 1.447 0.73 0.762 0.634 0.484 1.632 2.31 1.852 0.6013110002K08 TPR ST13 Mm.180337 Hs.377199 1.545 0.891 0.657 0.511 1.627 0.864 2.327 0.897 0.887 0.888 0.738 1.254 1.255 0.994 1.286 0.818 0.888 0.755 0.306 1.822 2.589 1.858 1.5592610511O17 TPR FLJ20272 Mm.209503 Hs.26090 1.511 1.025 1.01 0.922 2.436 1.5 1.727 1.076 3.665 3.531 3.856 1.895 2.872 1.65 3.043 1.489 2.218 3.035 3.021 2.583 2.688 2.497 1.2254831420N21 TPR OGT Mm.259191 Hs.405410 1.435 1.321 0.507 0.417 1.327 1.824 1.555 2.141 1.114 0.587 0.988 0.989 1.202 1.53 1.009 1.487 1.484 1.093 1.317 1.353 1.895 0.907 0.4162310038F17 TPR RAPSN Mm.1272 Hs.81218 2.175 2.086 0.763 0.809 0.801 1.354 0.438 0.282 2.859 1.182 1.949 1.424 3.35 1.004 1.279 1.172 1.667 1.341 2.85 2.835 3.836 0.856 0.3664932412G04 TPR RNF127 Mm.259741 Hs.144266 2.533 1.236 1.342 0.941 1.096 1.605 1.463 0.918 1.931 2.217 2.81 1.199 2.541 1.477 2.079 1.901 1.22 1.619 1.814 1.903 3.229 1.24 1.0732410081M15 BTB/POZ ZBTB8 Mm.32997 Hs.129837 2.901 1.567 0.954 1.843 0.705 1.886 1.003 1.086 1.344 1.245 1.949 1.976 2.043 1.548 0.796 1.198 1.078 0.923 1.382 2.891 3.952 0.613 1.3131200009E17 BTB/POZ SPOP Mm.285454 Hs.129951 1.367 0.825 1.049 0.643 0.6 1.265 0.606 0.441 0.764 1.16 0.571 1.151 1.276 0.641 0.442 0.844 0.854 0.532 0.385 1.748 1.446 0.89 0.9621700017G21 BTB/POZ 1700017G21 Mm.312625 2.724 1.826 2.097 1.705 1.042 1.715 1.085 0.729 2.862 3.308 3.099 2.21 3.282 1.342 1.511 1.704 2.236 1.597 2.415 2.325 2.551 0.568 0.7982810049M13 BTB/POZ BTBD14B Mm.289698 Hs.185254 1.794 1.728 0.462 1.818 1.021 1.62 0.515 0.641 1.078 0.888 0.826 1.629 2.501 0.81 0.871 1.055 1.218 0.682 1.054 2.119 2.859 0.503 0.6552810011C24 BTB/POZ MYNN Mm.200378 Hs.507025 1.168 0.986 0.947 0.695 0.975 2.2 0.577 0.32 1.417 2.096 0.882 1.095 1.581 1.43 0.749 1.335 1.312 0.74 1.127 2.846 0.327 0.778 1.4762700038B03 BTB/POZ SBBI26 Mm.273768 Hs.376793 0.841 0.944 0.684 0.417 0.868 1.229 0.697 0.743 0.796 1.223 0.887 1.034 1.405 0.779 0.535 1.013 1.327 0.842 0.962 1.048 1.489 0.382 1.1382610109I01 BTB/POZ ZNF131 Mm.139115 Hs.97845 1.129 0.861 1.07 0.803 0.887 1.499 1.134 0.843 1.169 2.047 1.387 1.073 1.766 1.392 1.1 1.247 1.456 1.126 1.408 1.305 1.344 0.766 1.6512610019F01 BTB/POZ BTBD4 Mm.56581 Hs.437574 1.237 0.797 1.298 0.796 0.597 1.248 0.828 0.636 1.763 2.239 1.279 2.023 1.267 2.096 1.029 1.225 1.352 1.568 1.497 1.695 0.998 0.037 0.6282210011M23 BTB/POZ ENC1 Mm.241073 Hs.104925 2.411 1.332 1.658 2.044 0.532 1.326 0.618 0.856 4.019 3.256 3.569 2.95 2.759 1.733 2.104 1.608 2.06 1.558 2.352 1.79 1.53 0.055 0.6371700126I16 BTB/POZ IVNS1ABP Mm.33764 Hs.197298 0.818 0.915 1.376 0.775 0.996 2.31 1.001 0.959 1.159 2.749 1.483 1.611 1.731 1.526 1.442 1.384 1.481 1.235 0.998 1.482 1.533 0.811 1.1541700010E06 BTB/POZ ZNF297B Mm.44186 Hs.376585 1.132 0.955 0.711 0.846 0.49 0.718 0.931 1.009 0.607 0.695 0.398 1.313 2.02 1.039 0.565 0.815 1.055 0.624 0.841 1.153 1.711 0.1 0.8132510026C23 BTB/POZ KBTBD4 Mm.279804 Hs.440695 2.109 1.653 0.771 1.321 1.916 2.005 0.809 0.965 1.829 2.824 2.626 1.981 2.852 1.055 0.981 1.325 1.459 1.21 1.86 1.616 2.043 0.044 1.1982610037C03 BTB/POZ BTBD2 Mm.60720 Hs.369288 1.638 1.392 0.799 0.759 0.451 0.979 0.528 0.58 1.818 3.236 1.384 2.017 3.653 0.933 1.004 1.055 2.056 1.187 1.263 1.492 1.594 0.215 0.4942810406K13 BTB/POZ FLJ33790 Mm.153585 Hs.292451 1.172 1.166 1.278 0.764 2.566 2.93 1.364 1.52 3.047 6.756 2.877 2.435 2.772 2.99 3.099 2.34 1.779 1.471 1.464 1.247 1.152 0.158 1.211200011O19 BTB/POZ FLJ13057 Mm.74594 Hs.243122 0.993 1.551 1.973 0.431 0.671 1.513 1.068 1.369 1.183 1.691 1.316 2.047 0.715 1.377 0.825 1.648 1.426 1.719 2.023 1.847 0.74 1.092 2.5064931401E10 BTB/POZ BTBD5 Mm.248678 Hs.99398 1.221 1.733 0.695 0.455 1.566 1.874 0.843 1.042 1.706 1.784 1.908 1.95 0.895 1.234 1.393 1.244 1.763 1.524 1.373 2.004 1.789 0.992 2.705

Page 22: New High-Throughput Mapping of a Dynamic Signaling Network in … · 2005. 3. 11. · Science Supporting Online Material Barios-Rodiles, p. 1 Science Supporting Online Material High-Throughput

1190005H08 BTB/POZ BTBD1 Mm.296945 Hs.321501 1.693 1.227 1.879 0.53 1.013 1.443 0.593 0.926 2.6 2.289 2.352 1.94 1.207 1.367 1.955 1.452 2.257 1.876 1.978 2.208 1.697 0.545 0.751300013C10 BTB/POZ KLHL1 Mm.125006 Hs.106808 1.779 1.224 1.068 0.493 1.146 1.236 1.163 1.283 3.549 3.54 2.489 1.968 1.111 2.358 1.859 2.205 2.618 2.646 3.903 2.782 1.426 0.767 0.7721200013C18 BTB/POZ KEAP1 Mm.248266 Hs.57729 1.405 1.712 1.593 0.505 0.941 1.185 0.76 1.413 0.941 1.02 0.748 1.888 0.76 1.317 0.917 1.442 0.929 1.071 1.291 1.7 1.617 0.827 0.9392310024D23 BTB/POZ KBTBD5 Mm.45734 Hs.350288 0.797 1.523 0.887 0.517 0.898 1.328 0.77 0.855 0.452 0.737 0.5 1.765 0.721 0.894 0.722 0.959 0.977 1.219 1.669 1.671 0.937 1.29 2.3481200009K10 BTB/POZ Bklhd2 Mm.224306 Hs.348262 0.786 0.994 0.737 0.226 0.446 1.096 0.181 0.294 1.149 1.401 1.243 1.489 0.711 0.724 0.716 0.866 0.972 0.959 0.752 0.864 0.913 0.208 0.4312900016J09 BTB/POZ RB1 Mm.273862 Hs.408528 0.776 0.609 1.526 0.225 0.68 2.17 0.614 1.09 0.598 1.429 0.705 1.005 0.53 0.698 0.758 0.979 1.226 1.173 0.908 1.667 1.044 0.708 1.5124930429H24 BTB/POZ DRE1 Mm.274579 Hs.246875 1.269 0.97 0.731 0.388 0.68 1.196 0.577 0.701 1.932 1.97 1.363 1.853 0.763 1.098 1.42 1.536 1.733 1.773 1.944 2.25 1.757 1.139 0.5511200003E21 BTB/POZ LZTR1 Mm.161726 Hs.78788 1.981 1.635 1.971 0.476 1.561 2.706 0.849 0.845 2.06 1.384 2.402 1.513 0.972 1.589 1.035 1.592 3.229 2.707 3.04 2.178 1.46 0.838 0.7451300017A20 BTB/POZ ZNF288 Mm.211212 Hs.436987 0.761 1.075 0.687 0.189 0.424 0.733 0.43 0.548 0.706 0.633 0.513 1.297 0.615 1.059 0.634 0.779 0.798 0.733 0.682 1.1 0.952 0.359 0.2432610021A10 PH SCAP2 Mm.156651 Hs.410745 1.846 0.934 1.765 0.644 1.061 1.877 1.43 1.161 1.981 5.671 2.515 1.509 1.1 1.707 2.655 1.796 1.643 2.153 1.26 1.423 1.539 0.745 1.0716430512N22 PH PLEKHA2 Mm.261122 Hs.470847 2.359 2.089 0.893 1.734 1.77 1.509 0.591 0.697 1.513 2.46 1.352 1.788 2.411 0.907 0.937 1.018 1.632 1.144 1.716 2.653 2.501 0.777 1.038A430106A18 PH ITK Mm.274218 Hs.211576 1.288 1.01 0.9 0.768 1.083 3.051 0.316 0.297 2.722 3.858 2.575 1.183 2.322 1.281 1.168 1.671 1.674 1.069 1.775 1.419 1.333 0.672 0.9784933426D16 PH SNTG1 Mm.129083 Hs.388360 1.999 0.986 0.896 0.716 1.75 2.715 1.317 1.171 4.105 5.578 4.922 1.863 2.84 1.946 1.967 2.399 2.613 2.167 1.413 1.445 1.977 0.566 1.095730427K19 PH APS Mm.277333 Hs.371366 1.066 0.98 1.086 0.586 1.459 1.322 1.331 1.581 1.266 2.639 1.294 1.222 1.637 1.183 0.869 1.18 1.321 1.036 1.206 0.836 0.964 0.692 1.21810074L23 PH PLEK Mm.98232 Hs.77436 1.632 1.105 0.395 0.847 1.328 1.124 0.808 1.432 2.168 4.887 1.538 1.9 0.39 4.839 1.626 2.005 1.556 2.263 2.331 1.653 1.164 0.796 1.3662010320F03 PH PLEK2 Mm.103380 Hs.170473 1.274 0.977 0.311 0.688 0.369 0.556 0.655 0.45 0.671 0.873 1.26 1.38 1.117 1.3 0.732 0.922 0.799 0.671 0.813 1.705 1.149 0.541 0.6051500001N23 PH PLEKHB1 Mm.26633 Hs.445489 2.992 2.073 1.442 2.062 2.139 2.276 1.005 0.469 14.25 11.13 9.533 3.467 3.8 3.156 6.678 3.765 11.27 7.287 5.948 2.794 2.873 0.951 1.2181200014M06 PH OSBPL3 Mm.44153 Hs.197955 2.637 2.139 0.877 2.215 1.62 2.457 0.611 0.75 2.105 2.58 1.357 2.323 3.05 1.616 1.544 1.168 2.725 2.016 2.78 4.503 3.796 1.188 1.4261200004I24 PH ARHGEF3 Mm.207446 Hs.25951 1.599 1.412 0.818 1.116 0.944 1.014 1.377 0.382 1.338 1.353 0.803 1.858 2.798 1.174 0.96 1.05 1.404 0.821 1.293 2.831 2.932 0.143 2.1243110056A02 PH POLR2J2 Mm.127418 Hs.406505 2.224 1.497 0.824 1.7 1.613 2.256 1.091 1.307 2.33 3.155 2.047 2.207 4.227 2.27 2.447 2.394 2.77 2.337 2.12 2.489 2.597 0.166 1.9164933433D06 PH OSBPL10 Mm.259777 Hs.368238 1.447 1.361 0.612 0.866 0.614 0.693 0.558 0.665 1.35 1.49 1.099 1.012 2.284 0.868 0.484 1.004 1.379 0.534 1.063 1.579 1.524 0.215 0.6822410043H07 PH PSCD2 Mm.272130 Hs.8517 0.884 1.155 0.452 0.667 0.445 0.65 0.414 0.297 0.773 0.89 0.848 0.946 0.926 0.947 0.79 0.916 0.809 0.51 1.148 1.047 1.106 0.339 1.3572810471M23 PH FLJ12604 Mm.235383 Hs.126485 2.692 2.258 1.624 2.315 1.033 2.074 0.849 0.75 14.97 12.47 10.01 4.559 0.171 6.022 3.777 3.512 2.163 2.974 3.465 2.038 2.522 0.843 1.1899530063M10 PH GNRPX Mm.41479 Hs.512626 1.774 1.44 0.783 1.428 1.026 1.327 0.617 0.761 3.724 3.575 2.896 2.225 1.978 3.458 2.511 1.82 1.933 1.706 1.388 1.642 1.475 0.062 0.946230420N16 PH FLJ12987 Mm.255342 Hs.296730 1.708 1.022 1.058 0.951 0.766 1.755 0.625 0.793 1.852 3.664 1.873 1.496 1.771 1.397 1.578 1.316 1.296 1.359 1.269 1.422 1.32 1.026 1.0165031433E13 PH SWAP70 Mm.282528 Hs.153026 1.021 0.969 0.502 0.794 1.024 1.039 1.273 0.624 1.692 2.843 1.58 1.345 1.305 1.366 1.284 1.141 0.936 0.57 0.728 1.549 1.995 0.715 1.3414933427A08 PH FGD6 Mm.269596 Hs.170623 1.615 1.143 0.394 0.89 0.791 1.35 1.028 0.94 1.343 2.055 1.081 1.52 1.96 1.508 3.109 2.236 1.185 0.805 0.856 1.488 2.402 0.781 1.3129130014M22 PH FLJ10244 Mm.28376 Hs.220745 2.535 2.141 0.527 1.623 1.116 1.707 0.728 0.611 5.631 10.26 5.098 2.281 3.624 1.48 2.99 2.771 3.99 2.998 4.006 4.269 4.362 0.863 1.0665830480G12 PH ARHGAP15 Mm.239239 Hs.433597 0.758 1.051 0.796 0.705 0.723 0.997 0.935 1.024 2.743 4.376 3.118 1.405 1.751 1.14 1.263 1.305 1.603 1.086 0.929 3.843 3.234 1.404 2.072810487K11 PH PSCD3 Mm.281003 Hs.7984 0.834 1.013 0.21 0.846 0.41 0.572 0.149 0.166 0.675 0.539 0.642 0.829 1.052 0.687 0.666 0.664 0.567 0.313 0.424 1.568 1.312 0.762 0.462410008H17 PH GEFT Mm.22583 Hs.61581 2.231 2.002 1.055 1.301 0.802 1.296 0.493 0.556 2.535 2.928 2.355 2.123 3.569 1.275 1.224 1.215 2.485 1.572 1.31 1.457 1.877 0.414 1.072810052M02 PH CKIP-1 Mm.29475 Hs.173380 1.457 1.661 0.976 1.79 0.472 0.601 0.213 0.335 0.739 0.534 0.381 1.79 1.196 1.959 0.62 1.222 0.731 0.708 0.53 6.305 3.667 1.767 0.4761700038J06 PH ARHGEF6 Mm.261443 Hs.372800 3.038 1.758 1.866 3.019 1.921 2.642 0.971 0.873 3.654 3.059 2.503 4.944 3.879 1.748 2.095 1.56 2.252 1.76 3.261 2.313 2.504 0.942 0.4811300015B16 PH DNM2 Mm.39292 Hs.432832 0.805 0.695 0.664 0.446 0.467 0.582 0.276 0.289 0.57 0.448 0.474 0.9 0.826 0.703 0.467 0.69 0.689 0.386 0.777 1.361 1.217 0.411 0.5450610010K16 PDZ RGS19IP1 Mm.20945 Hs.6454 0.717 0.59 0.966 0.472 0.388 0.518 0.853 0.718 0.879 0.876 0.372 1.46 0.13 1.949 0.687 1.165 0.909 1.138 1.14 1.227 1.086 0.659 1.1242610024J09 PDZ AUP1 Mm.275961 Hs.411480 1.075 0.767 0.662 0.774 0.37 0.521 0.538 0.568 1.848 2.592 0.984 2.09 1.29 1.348 1.025 1.168 2.312 1.209 1.554 1.2 0.803 0.17 0.4482700099C19 PDZ LOC51248 Mm.291607 Hs.11042 1.267 0.56 1.276 0.457 0.445 1.478 0.863 0.988 0.64 0.797 0.674 1.195 1.194 1.225 0.694 0.868 1.111 0.838 1.006 1.202 1.322 1.086 1.4784833411E15 PDZ SDCBP Mm.247473 Hs.164067 0.945 0.861 0.754 0.583 0.661 1.101 0.528 0.821 0.606 0.998 0.654 1.156 1.189 0.921 0.631 0.851 0.847 0.584 0.544 0.931 1.638 0.472 0.8834921513F16 PDZ PDZK1 Mm.28015 Hs.15456 1.116 0.701 0.748 0.455 0.464 1.27 0.718 0.758 0.678 1.191 0.457 0.961 1.344 0.842 0.587 0.89 1.104 0.638 0.899 1.149 1.578 0.832 1.1261300011C24 PDZ TIP-1 Mm.186 Hs.12956 0.659 0.557 0.567 0.323 0.306 0.831 0.723 0.776 0.755 0.801 0.54 0.961 1.087 0.96 0.434 0.805 0.851 0.51 0.451 0.737 0.854 0.313 1.0452900002D01 PDZ FLJ10490 Mm.2535 Hs.221737 1.124 0.958 0.325 0.681 0.38 0.368 0.316 0.825 0.651 0.591 0.361 2.072 0.707 2.054 0.693 1.217 0.671 0.839 0.501 1.016 0.655 0.422 0.5271110001A05 PDZ LIM Mm.117709 Hs.154103 0.527 0.657 0.952 0.557 0.822 1.302 0.838 1.22 1.045 0.873 0.907 1.254 0.964 1.731 0.844 1.164 0.99 0.614 1.113 1.045 1.388 0.179 1.9382900002K10 PDZ SYNJ2BP Mm.279603 Hs.443661 1.656 1.55 1.384 0.878 1.186 1.17 0.366 0.606 2.365 1.754 1.931 1.531 2.085 2.238 2.631 2.038 2.001 1.374 1.917 1.577 1.527 0.222 0.8280610011L07 PDZ SLC9A3R2 Mm.21587 Hs.440896 1.367 1.324 0.895 1.194 1.008 1.506 0.643 0.81 0.738 0.861 0.458 1.169 2.21 1.148 0.841 0.833 0.807 0.647 1.158 1.235 2.115 0.757 1.5831110032B18 PDZ LDB3 Mm.29733 Hs.49998 1.101 0.732 0.738 0.474 0.948 1.115 0.7 0.635 0.882 1.238 0.645 0.882 1.341 0.924 0.877 0.957 1.258 0.379 1.267 1.003 1.49 0.861 1.5652610202L11 PDZ PSMD9 Mm.30237 Hs.131151 1.962 2.096 0.586 1.014 1.117 1.731 0.825 0.915 0.71 1.425 0.609 1.332 2.061 1.146 0.727 1.012 1.035 0.63 0.251 1.131 1.593 1.113 2.3740710008C04 PDZ PARD6A Mm.250566 Hs.112933 1.807 2.072 1.216 1.273 0.733 1.078 0.73 0.965 2.388 5.004 2.191 1.418 2.956 1.47 2.556 1.723 1.998 1.337 2.026 1.144 1.725 0.624 0.8479130022D09 PDZ LIN7C Mm.235300 Hs.91393 0.875 0.966 0.827 0.606 1.368 1.307 0.875 1.37 1.103 1.428 1.218 1.303 1.459 1.309 1.073 1.245 1.094 0.79 0.809 1.013 1.003 0.614 2.1092200002N01 PDZ GIPC2 Mm.97 Hs.147975 1.448 0.769 0.171 0.727 0.829 1.221 0.914 0.733 0.728 0.437 0.555 1.165 1.185 0.731 0.764 0.872 1.345 0.8 1.554 1.521 1.28 0.735 1.0934930506N09 PDZ RGS3 Mm.286753 Hs.82294 3.265 2.822 1.599 3.179 2 1.967 1.256 1.275 1.437 1.804 1.06 3.931 4.914 1.338 1.073 1.077 1.619 0.962 0.557 2.029 2.035 0.815 1.5014931400F03 PDZ GRIP1 Mm.196692 Hs.372377 3.547 3.499 1.167 2.318 1.333 2.302 0.787 0.811 1.198 2.113 0.872 1.499 1.972 1.364 1.024 1.417 1.296 0.964 1.081 1.806 3.666 1.25 1.2232010002N16 PDZ ALS2CR19-v1 Mm.35593 Hs.26981 1.471 2.146 1.242 0.662 1.354 1.597 0.548 0.72 0.836 1.553 1.334 1.417 0.724 0.886 0.872 1.11 0.867 0.985 1.286 15.77 9 1.114 1.757AB029485 PDZ Acvrinp1 Mm.319105 Hs.22599 1.643 1.457 1.359 1.132 2.504 1.337 0.995 1.177 0.707 0.81 0.58 1.379 1.26 1.554 0.892 1.21 1.27 1.013 1.178 1.926 1.54 0.745 0.1111700011C14 phosphatase MK-STYX Mm.247666 Hs.11615 0.735 0.953 1.153 0.322 1.074 1.65 0.423 0.577 2.033 3.275 1.602 1.304 0.72 0.964 2.113 1.455 1.406 1.251 0.729 2.449 2.226 0.585 1.0532610306G15 phosphatase DUSP10 Mm.266191 Hs.177534 1.376 0.847 1.037 0.287 0.924 0.691 0.26 0.653 1.53 3.026 1.383 2.529 0.899 1.464 1.496 1.401 1.258 1.334 1.185 1.104 1.792 1.111 0.7651700022L10 phosphatase DUSP13 Mm.52571 Hs.178170 1.045 1.33 0.888 0.29 1.033 0.859 0.529 0.751 1.237 1.43 1.053 1.313 0.514 1.206 0.657 1.162 0.756 0.758 0.557 1.872 1.227 0.974 0.7044930527G07 phosphatase DUSP18 Mm.32588 Hs.128782 0.839 0.99 0.787 0.213 0.576 0.814 0.482 0.639 0.58 0.963 0.454 1.268 0.444 0.87 0.687 0.963 0.589 0.633 0.443 0.613 0.538 0.574 1.0712210015O03 phosphatase DUSP3 Mm.196295 Hs.181046 1.659 2.029 1.337 0.405 2.209 1.98 0.565 0.641 0.634 0.961 0.943 1.498 0.85 0.904 0.973 1.051 1.178 0.91 0.744 1.525 1.42 1.397 1.5192310042C07 phosphatase DUSP14 Mm.240885 Hs.91448 1.008 0.935 0.754 0.257 0.644 0.985 0.344 0.476 0.862 1.137 1.064 1.205 0.533 0.695 0.634 0.972 0.697 0.747 0.469 1.22 1.551 0.825 0.2592310043K02 phosphatase DUSP13-like Mm.52571 Hs.178170 2.203 1.499 1.08 0.664 1.948 2.272 1.053 0.584 5.773 5.843 4.675 2.135 1.25 3.158 3.68 4.21 2.788 2.757 2.385 3.362 2.941 0.837 0.7471700094E07 phosphatase 1700094E07Rik Mm.159027 1.396 1.093 1.039 0.429 2.173 1.945 0.638 0.751 1.69 2.408 1.698 1.24 0.669 1.321 1.243 1.46 1.743 1.443 1.613 1.77 1.904 1.045 0.6250610039A20 phosphatase STYX Mm.202561 Hs.364980 0.986 0.96 0.419 0.303 1.478 2.405 0.72 0.99 1.259 0.963 1.222 1.187 0.64 0.857 0.912 1.095 1.073 1.208 1.104 1.564 1.37 0.796 0.8421300019I03 phosphatase DUSP6 Mm.1791 Hs.298654 1.261 1.089 1.368 0.472 2.211 1.117 0.584 0.935 1.479 3.611 1.153 2.299 1.071 2.322 1.986 2.311 1.267 1.369 0.76 0.492 0.997 0.786 0.2831190004O14 phosphatase DUSP12 Mm.34365 Hs.416216 1.286 1.213 1.234 0.297 1.04 1.054 0.621 0.818 0.84 0.943 0.673 1.981 0.718 1.37 0.803 1.257 0.937 1.03 0.778 1.469 1.005 0.754 0.4871600009O09 phosphatase ILKAP Mm.234179 Hs.92033 1.324 2.084 0.564 0.93 3.046 1.813 1.272 1.473 5.844 8.503 5.765 1.627 1.949 1.637 3.953 3.238 2.158 3.274 2.805 1.862 2.454 1.456 0.6752410007M08 phosphatase PPM1A Mm.261045 Hs.130036 0.932 1.006 0.664 0.512 2.425 0.859 1.056 1.131 0.501 2.007 0.474 1.092 1.199 1.193 0.853 1.393 0.859 0.701 0.974 1.288 1.124 0.965 0.8584921535M01 phosphatase PPP3CC Mm.1567 Hs.75206 1.69 1.618 1.334 1.252 1.941 1.653 1.68 1.714 3.077 5.499 2.699 1.667 1.747 2.653 2.555 2.511 2.283 3.013 1.375 2.186 1.989 1.155 0.1861810062E21 phosphatase PPP1CA Mm.277629 Hs.183994 1.202 1.369 0.849 0.475 0.722 0.621 0.488 0.674 2.778 3.125 1.666 1.03 2.007 1.582 1.125 1.536 1.627 1.408 2.29 1.931 1.9 1.143 0.0232810407I23 phosphatase PPP2CA Mm.260288 Hs.91773 1.859 1.737 1.482 0.718 0.966 2.198 1.223 1.246 2.621 1.909 2.054 1.276 2.543 1.477 1.687 1.528 1.702 1.31 3.053 1.069 2.346 2.157 1.7682610028M06 phosphatase PPP1CC Mm.280784 Hs.79081 0.836 1.268 0.697 0.389 0.494 0.911 0.461 0.325 1.521 1.707 1.778 1.103 1.616 0.717 0.722 0.999 1.13 0.766 0.926 1.18 1.674 1.539 0.3732310003C10 phosphatase PPP6C Mm.25345 Hs.356739 1.799 1.241 0.647 0.798 1.401 2.549 1.802 1.68 1.92 3.195 4.364 1.404 2.309 1.503 1.54 1.585 2.152 2.387 2.967 1.623 2.339 2.233 1.3211200010B19 phosphatase PPP1CB Mm.241931 Hs.21537 1.387 1.052 0.963 0.689 0.772 1.578 1.469 0.451 1.441 2.226 1.876 1.735 2.604 1.126 2.315 1.108 1.943 2.071 2.36 2.262 3.113 2.329 0.7681200007O21 LIM NEBL Mm.120298 Hs.5025 1.393 1.032 0.436 0.568 0.711 1.802 0.837 1.317 0.52 1.073 0.615 0.84 1.034 1.112 0.714 0.87 0.788 0.737 0.365 1.048 0.703 0.704 1.2832810478G04 LIM LMO2 Mm.29266 Hs.283063 2.009 4.67 2.432 1.265 2.034 1.861 0.485 2.017 1.777 2.989 2.144 2.919 2.348 1.745 1.205 1.381 1.769 1.416 2.679 2.417 1.605 0.883 0.6932210410P18 LIM LMCD1 Mm.234441 Hs.279943 1.676 1.262 1.274 0.657 0.533 0.239 0.805 0.994 0.932 1.111 1.474 1.433 1.441 1.054 0.77 0.904 0.956 0.82 1.201 1.666 0.942 0.67 0.5854921524A02 LIM LIMS1-v1 Mm.57734 Hs.112378 1.06 1.468 2.945 0.824 0.851 1.542 1.151 1.069 9.791 4.467 9.059 1.782 1.483 1.416 1.475 1.32 1.751 1.723 2.938 4.309 2.81 2.134 0.643

Page 23: New High-Throughput Mapping of a Dynamic Signaling Network in … · 2005. 3. 11. · Science Supporting Online Material Barios-Rodiles, p. 1 Science Supporting Online Material High-Throughput

2810049E20 LIM LHX9 Mm.250732 Hs.442578 3.325 3.315 2.969 1.472 1.39 1.898 1.102 0.821 2.743 2.65 2.788 2.323 1.981 1.571 1.628 1.825 1.453 1.455 2.377 5.125 3.26 0.873 0.807E130113K05 LIM CSRP1 Mm.196484 Hs.108080 1.74 1.988 1.994 0.739 1.02 1.107 1.384 1.023 0.708 0.74 0.54 1.698 1.68 1.357 0.764 1.284 0.877 0.998 1.012 1.258 1.485 0.725 0.5840610010I23 LIM CRIP2 Mm.294801 Hs.70327 1.898 1.617 2.681 0.704 0.945 1.684 1.011 1.185 0.723 1.686 0.713 1.549 1.533 1.275 0.54 1.528 1.057 0.989 0.987 1.508 1.166 1.026 0.7832810002M14 LIM CSRP2 Mm.2020 Hs.10526 1.827 2.072 1.644 0.838 1.015 1.748 1.475 0.992 1.333 1.362 1.209 1.574 1.586 1.409 0.724 1.695 1.03 0.914 0.395 1.595 1.222 0.596 0.7962310016J22 LIM LIMS1-v2 Mm.57734 Hs.112378 1.722 1.747 0.979 0.881 1.148 1.645 1.6 1.474 1.025 1.393 1.454 2.047 1.486 2.445 0.833 1.665 0.795 1.233 1.001 1.891 1.204 0.857 0.6612610509F17 LIM JUB Mm.100253 Hs.434997 0.889 0.675 0.308 0.529 0.664 0.26 1.287 0.977 2.547 0.814 0.64 1.637 0.259 4.586 0.636 1.723 1.492 2.258 1.744 1.38 0.694 0.318 1.0332610507L09 LIM CRIP1 Mm.272368 Hs.423190 0.855 0.903 1.165 0.815 0.719 0.945 1.008 0.886 1.321 1.15 0.716 1.849 1.105 1.617 0.511 1.08 1.023 0.79 1.43 1.076 0.832 1.366 1.5411700027G07 LIM FHL5 Mm.87325 Hs.283689 2.176 1.939 1.801 2.391 0.918 1.268 1.002 0.886 2.235 1.569 1.499 3.163 2.546 1.227 0.748 1.122 1.511 1.286 0.518 1.738 2.134 0.736 1.0611700010N06 LIM FHL1 Mm.46163 Hs.421383 0.987 0.503 0.674 0.596 0.801 1.427 0.741 0.671 0.542 0.585 0.325 1.298 1.09 0.632 0.467 0.746 0.916 0.733 0.495 0.94 0.871 0.807 0.9152410007B04 LIM TRIP6 Mm.27063 Hs.380230 2.99 2.371 1.714 2.744 2.125 2.366 1.063 0.965 1.499 1.344 1.41 2.501 4.018 1.169 1.01 1.443 1.539 0.693 1.205 1.403 2.391 0.923 1.192610029O20 LIM CSRP3 Mm.17235 Hs.83577 1.251 1.324 0.438 1.058 0.222 0.355 0.558 0.524 0.576 0.562 0.479 1.75 1.733 0.763 0.533 0.786 0.926 0.462 0.521 0.873 1.418 0.707 0.9016720456D19 LIM ALP Mm.282900 Hs.71719 0.52 0.854 0.862 0.556 0.755 1.04 0.813 1.123 0.633 0.981 0.8 1.279 1.217 0.83 0.395 0.969 0.969 0.554 0.587 0.903 0.785 0.619 1.8752410002J21 LIM ENIGMA Mm.275648 Hs.436339 1.133 1.484 0.773 1.067 0.651 1.362 0.611 0.905 0.767 0.969 0.565 1.042 1.592 0.879 0.718 0.82 0.867 0.486 0.565 1.329 1.375 1.064 1.4084931439A04 zf-C3HC4 DKFZp434J0617 Mm.120835 Hs.104744 1.468 1.354 1.075 1.373 3.044 1.139 1.215 1.374 1.735 2.58 2.167 1.901 1.655 1.267 2.281 1.384 1.614 1.856 1.023 2.608 2.857 1.276 0.245A430106H13 zf-C3HC4 TRIM35 Mm.288225 Hs.137732 3.447 5.282 1.49 3.96 6.655 1.779 1.287 0.974 1.877 2.177 1.048 8.776 6.398 1.173 0.908 1.268 1.377 1.733 0.985 2.968 3.925 1.79 0.6322610509H23 zf-C3HC4 RNF146 Mm.28930 Hs.267120 1.683 2.145 0.381 1.46 2.828 0.981 1.532 1.39 0.809 1.555 3.722 1.857 1.577 1.473 0.928 0.849 1.17 1.251 1.024 2.312 1.973 2.103 0.4092610005D23 zf-C3HC4 RNF14 Mm.22086 Hs.170926 2.488 2.766 1.998 2.719 3.053 1.435 1.716 1.35 2.238 2.688 2.38 3.284 2.913 1.582 1.083 1.479 1.797 1.903 0.691 4.186 4.433 3.97 1.0622700043E10 zf-C3HC4 RNF2 Mm.31512 Hs.124186 1.903 1.801 1.445 1.704 2.587 2.479 1.724 1.727 2.267 2.576 1.903 1.844 2.35 1.108 1.973 1.473 1.667 1.366 0.83 2.34 2.602 4.622 0.7682310043C01 zf-C3HC4 TRIM34 Mm.26466 Hs.125300 0.991 1.493 1.347 0.756 1.693 0.994 1.196 1.224 0.983 1.088 1.196 1.018 0.998 1.38 1.299 1.054 1.627 1.098 1.403 1.514 1.614 1.015 0.0832510042A13 zf-C3HC4 Rnf130 Mm.166372 Hs.525059 0.603 0.923 0.317 0.765 0.981 1.115 0.736 0.815 10.74 9.688 15.27 1.57 1.147 1.2 2.315 0.914 1.661 1.402 0.966 1.759 2.134 1.333 2.5832610110L04 zf-C3HC4 RNF141 Mm.268926 Hs.44685 1.737 1.723 2.479 1.824 2.026 1.014 1.364 0.944 1.016 0.929 0.866 2.117 2.138 1.074 1.16 1.116 1.207 1.038 1.033 1.891 4.398 1.185 0.1252810430O10 zf-C3HC4 RNF12 Mm.44069 Hs.122121 0.998 1.195 0.982 1.123 1.263 0.886 0.577 0.553 0.781 1.542 0.802 1.624 1.333 1.011 0.973 0.984 1.058 0.998 0.54 3.447 4.415 1.489 0.0753110001L12 zf-C3HC4 RFP2 Mm.23959 Hs.436922 1.15 1.308 0.855 1.204 2.295 0.705 1.219 1.288 1.762 2.264 2.628 1.482 1.356 1.81 1.506 1.74 1.824 1.792 0.508 2.399 2.581 1.331 0.0882410015A17 zf-C3HC4 RNF138 Mm.253542 Hs.180403 2.259 2.268 2.083 2.814 3.227 1.615 0.949 0.896 2.579 3.79 1.355 3.604 3.283 1.349 1.549 1.084 1.354 1.67 0.924 2.829 4.669 1.357 0.3621300004G08 zf-C3HC4 FLJ23360 Mm.267353 Hs.161279 2.669 3.079 1.757 2.706 2.525 1.586 1.351 0.884 2.069 1.225 1.58 3.567 3.41 1.355 1.985 1.395 1.65 1.247 1.472 2.466 4.709 1.262 0.7622410131O05 zf-C3HC4 RNF5 Mm.274542 Hs.512071 1.081 1.282 0.401 1.041 2.124 0.938 1.343 0.995 3.498 2.882 2.571 2.179 1.653 1.669 1.984 1.655 1.717 1.895 1.111 2.773 1.512 1.815 0.724921523A11 SH3 NCK2 Mm.144978 Hs.101695 1.254 1.247 0.952 0.867 0.503 0.854 0.694 1.356 0.81 1.049 0.969 1.355 1.13 0.734 0.761 1.332 1.332 0.892 0.581 1.58 1.917 1.055 1.2981200007H22 SH3 SH3KBP1 Mm.167131 Hs.153260 0.838 0.834 0.413 0.428 0.473 0.373 1.325 1.473 0.475 0.649 0.514 0.99 0.897 1.257 0.48 0.841 0.669 1.126 3.001 1.391 0.801 0.84 1.1311600023G18 SH3 OSTF1 Mm.172222 Hs.47011 2.054 0.659 1.92 0.286 0.468 1.801 0.674 0.871 0.996 1.091 0.549 0.849 0.918 1.112 0.812 1.141 1.02 0.606 1.298 1.232 0.704 0.633 1.1722610511H05 SH3 SH3GL3 Mm.736 Hs.518629 0.861 0.627 0.765 0.212 0.553 1.534 1.28 1.521 0.991 1.152 0.473 0.749 0.814 1.102 0.711 1.107 1.352 1.126 1.42 1.072 0.936 0.611 1.1894632407K17 SH3 Tnnt1-v2 Mm.258670 Hs.411875 2.208 1.251 1.981 0.856 0.937 1.526 0.935 1.173 1.592 2.083 1.476 0.957 1.102 1.127 1.202 1.437 1.251 1.115 1.025 1.547 1.564 0.631 1.2264930572H05 SH3 SRGAP1 Mm.249576 Hs.408259 2.57 1.675 1.861 1.452 1.498 2.851 1.69 1.879 1.319 2.802 1.607 1.839 1.939 1.904 1.782 2.311 1.912 3.419 2.029 1.63 1.514 0.791 1.2126330413E15 SH3 PACSIN3 Mm.288732 Hs.334639 0.587 0.915 1.05 0.528 0.415 0.598 0.572 0.583 0.42 0.558 0.453 1.01 1.077 1.266 0.348 1.236 0.889 0.832 0.868 1.382 0.878 0.812 1.1218430435N19 SH3 GRAP Mm.202760 Hs.159517 0.932 1.175 0.632 0.34 0.289 0.792 0.358 0.331 1.695 2.085 1.649 0.844 0.901 1.029 0.815 1 1.056 0.897 1.232 0.77 0.527 0.392 0.3842310034C04 SH3 NOXO1 Mm.269293 Hs.191762 1.263 1 1.073 0.357 1.212 1.736 1.021 1.532 2.995 4.088 3.325 1.663 0.869 2.233 2.46 1.827 1.433 1.962 1.537 1.881 1.629 0.876 0.5751200013B08 SH3 CXorf9 Mm.276131 Hs.61469 2.386 2.505 1.392 1.985 4.301 1.37 2.259 3.281 1.451 2.781 0.953 1.548 1.792 2.737 2.233 2.213 1.455 0.954 3.429 1.485 3.678 1.475 0.7684930548L11 SH3 SAMSN1 Mm.131406 Hs.221851 0.482 0.927 0.536 0.654 2.511 1.467 1.112 1.339 0.994 2.192 1.124 1.11 0.846 1.253 1.282 1.277 1.159 1.525 1.015 1.197 1.515 1.629 0.4264632411K03 SH3 Tnnt1-v1 Mm.258670 Hs.411875 2.746 3.547 1.339 2.242 2.925 1.781 1.128 1.276 3.185 4.377 3.191 2.557 4.355 1.52 1.911 1.463 2.461 3.199 2.28 5.986 6.727 2.1 0.362610016A03 Acetyltransferase SAT2 Mm.20155 Hs.10846 1.297 1.571 1.98 1.148 1.941 1.057 1.045 1.091 3.83 4.078 2.845 1.873 1.842 1.501 1.343 1.304 1.199 2.33 1.103 1.802 2.657 1.249 0.110610011E04 Acetyltransferase SAT Mm.2734 Hs.28491 0.229 0.324 0.154 0.198 0.187 0.238 0.222 0.221 0.456 0.471 0.379 0.769 0.468 0.746 0.335 0.669 0.698 0.446 0.159 0.231 0.446 0.304 0.0710610037O16 Acetyltransferase NAT8 Mm.154782 Hs.14637 0.844 1.171 1.569 1.036 3.222 0.698 0.322 1.264 2.128 5.097 3.562 1.692 1.425 2.427 2.63 2.276 1.397 2.541 1.169 1.249 1.491 1.43 0.4172310039H09 Acetyltransferase ARD1 Mm.5934 Hs.433291 1.179 2.061 0.582 1.488 1.581 0.813 1.21 1.034 0.707 1.597 1.542 2.033 1.453 1.669 1.504 1.331 1.78 1.508 0.41 1.643 2.072 1.074 0.1372600005K24 Acetyltransferase MAK3P Mm.278726 Hs.288932 0.753 0.979 0.285 0.694 1.306 1.04 0.759 0.774 0.416 0.933 0.544 1.316 0.943 1.208 0.92 1.021 1.197 0.844 0.632 1.795 1.946 1.017 0.1092610507P14 Acetyltransferase ELP3 Mm.29719 Hs.267905 1.979 1.459 1.097 1.359 1.102 0.873 0.629 0.476 1.251 2.109 2.777 3.935 2.74 0.86 1.302 1.142 2.178 1.618 1.214 3.352 4.137 0.71 0.0751810018F03 Acetyltransferase Cml5 Mm.46315 Hs.458287 1.345 1.516 1.054 1.321 2.303 2.204 0.941 1.24 1.739 2.508 1.476 1.928 1.618 1.636 2.532 1.653 1.207 1.913 1.041 1.87 2.733 1.104 0.0851500004D14 Acetyltransferase NAT5 Mm.151168 Hs.109253 2.15 1.732 1.513 2.156 1.895 1.167 0.633 1.313 3.233 5.841 3.399 3.251 3.067 2.863 3.856 2.428 2.641 3.598 2.094 3.676 4.604 1.63 0.0821200013P24 Acetyltransferase FLJ14154 Mm.133257 Hs.312841 1.178 1.535 1.443 1.35 2.688 1.019 0.437 0.834 2.013 2.213 0.938 1.619 1.474 1.39 1.233 1.446 1.222 1.065 0.812 2.386 2.279 1.168 0.1381110028N05 Acetyltransferase DKFZP564C103 Mm.86823 Hs.144058 1.42 2.139 1.201 2.128 2.198 1.662 1.458 1.246 1.738 2.253 1.045 3.249 2.495 1.358 1.058 1.266 1.288 1.633 0.863 1.511 2.248 1.722 0.3721810043O14 Acetyltransferase GNPNAT1 Mm.233534 Hs.478025 0.684 1.257 1.008 0.632 1.434 0.756 1.764 1.131 1.592 1.343 0.901 1.489 1.253 1.144 0.648 1.221 0.78 0.953 0.689 1.932 1.5 0.882 0.6832810011M06 PHD ING1L Mm.272313 Hs.107153 1.202 2.174 1.036 1.91 1.763 1.264 0.276 0.791 2.139 2.385 1.06 3.121 1.352 2.353 0.937 1.194 0.896 1.356 1.57 14.08 7.932 3.262 1.4311300013A07 PHD ING3 Mm.39999 Hs.143198 1.24 1.148 1.648 1.54 1.39 1.895 1.049 0.848 2.386 1.999 1.431 2.218 1.669 2.49 1.542 1.657 1.446 1.268 0.867 2.298 1.781 0.911 1.6523321402G02 PHD DKFZP727G051 Mm.286766 Hs.119960 2.25 1.616 1.732 1.562 0.473 0.917 0.327 0.327 1.884 1.964 1.581 1.874 2.331 1.169 1.18 1.146 1.554 0.963 1.496 7.467 4.48 0.903 0.5342810027J24 PHD LOC57117 Mm.246726 Hs.432952 1.505 1.331 0.778 1.151 0.92 1.504 0.686 0.753 0.727 0.776 0.652 1.458 1.872 0.855 0.745 1.078 0.936 0.409 0.65 1.447 2.139 0.757 0.952410002I16 PHD CGBP Mm.17537 Hs.180933 1.197 1.206 0.651 0.795 0.533 0.687 0.2 0.226 1.018 0.86 0.651 0.79 1.084 0.664 0.432 0.804 0.862 0.497 0.732 3.425 2.469 0.572 0.5442410141M05 PHD MGC2941 Mm.20805 Hs.380734 1.532 1.226 0.6 0.988 0.565 1.018 0.171 0.932 0.805 1.153 1.406 1.169 1.837 1.052 0.835 1.12 1.035 0.636 0.477 1.856 2.513 0.392 0.8542600014C22 PHD PYGO1 Mm.273605 Hs.256587 1.185 1.042 0.472 0.873 1.115 2.089 0.811 0.253 0.968 2 0.546 0.977 1.773 1.357 0.955 1.003 1.146 0.603 1.124 1.138 1.68 0.655 0.9542310010G05 PHD ING4 Mm.262547 Hs.108183 1.179 1.142 0.418 0.77 1.336 1.556 0.163 0.64 0.987 1.188 0.718 1.574 2.129 0.948 0.854 1.009 1.167 0.622 0.648 1.572 1.166 0.552 0.9751200016G04 PHD DPF2 Mm.259204 Hs.13495 1.168 1.194 0.89 0.952 0.789 1.073 0.721 0.762 1.426 1.987 1.384 1.488 1.754 1.427 1.065 1.3 0.983 0.727 0.699 1.446 1.38 0.792 0.806D230038D11 PHD MLL5 Mm.205190 Hs.380021 0.396 0.519 1.051 0.392 0.417 1.175 0.979 1.334 0.558 1.184 1.202 1.36 1.004 1.926 0.628 1.242 1.076 1.017 1.923 1.011 0.721 0.918 0.7891300012O03 armadillo AP2B1 Mm.39053 Hs.370123 2.078 1.254 0.829 1.008 2.194 3.125 1.376 0.986 1.769 1.523 2.009 1.379 1.618 1.424 3.116 1.399 1.286 1.589 1.506 2.285 3.301 1.732 0.8064933431K05 armadillo RTDR1 Mm.67658 Hs.445808 2.112 1.22 1.053 1.01 1.709 3.785 0.921 0.828 1.085 1.12 1.142 1.368 1.737 0.929 1.561 0.933 0.88 0.831 0.968 1.025 2.411 1.504 0.8221300016C01 armadillo PKP2 Mm.2252 Hs.25051 1.371 1.785 1.201 0.938 0.461 1.073 0.452 0.295 1.058 0.675 0.691 1.129 1.443 0.74 1.168 0.753 0.977 0.715 0.814 2.685 2.943 1.535 0.4681500019G21 armadillo 1500019G21 Mm.305300 Hs.527950 1.983 2.495 0.665 1.4 1.171 1.057 0.628 0.399 1.066 0.926 1.189 1.255 1.529 0.68 1.035 0.781 1.04 0.994 0.728 1.568 1.285 1.565 0.5031200015K23 armadillo HSPC056 Mm.234823 Hs.102708 0.878 1.48 1.205 0.671 1.45 0.664 1.519 1.768 1.859 1.46 2.092 1.064 1.421 2.048 2.219 2.199 1.994 2.388 2.44 1.68 2.03 1.025 2.3421700007K14 armadillo SPAG6 Mm.31701 Hs.158213 0.976 1.212 0.695 0.508 0.937 1.594 0.813 0.682 1.114 0.624 1.209 1.01 1.217 0.993 0.936 1.132 1.148 0.836 0.432 1.677 2.945 1.669 1.2932410044B12 armadillo KPNA2 Mm.12508 Hs.252712 0.605 0.685 0.626 0.666 0.525 0.837 0.909 0.622 0.717 0.849 0.656 1.008 0.843 0.76 1.039 0.843 0.953 0.878 0.809 1.781 1.98 2.102 1.0552310016N05 armadillo FLJ10511 Mm.200383 Hs.106768 0.553 1.454 0.676 0.461 0.717 1.001 0.344 0.632 1.314 1.814 0.869 1.013 1.282 1.481 1.544 1.383 1.042 0.885 0.818 1.341 1.467 1.294 0.914X87838 armadillo CTNNB1 Mm.291928 Hs.410086 0.95 0.882 1.624 0.92 1.716 1.404 0.741 0.763 0.705 0.926 0.759 1.448 1.12 1.065 0.995 1.195 0.986 0.704 0.919 1.615 1.973 0.375 0.1451300018I05 WW KIAA0082 Mm.296974 Hs.202331 1.121 1.647 0.827 0.552 0.637 1.025 0.662 0.726 1.068 1.111 1.304 1.386 1.55 1.734 0.669 1.724 1.384 1.312 0.869 1.057 0.941 0.654 0.3260610025L01 WW PIN1 Mm.7906 Hs.161362 0.574 1.179 0.916 0.317 0.834 0.738 0.214 0.839 0.632 0.624 0.406 0.89 0.949 1.404 0.638 1.371 1.977 1.329 2.354 0.91 0.557 0.833 0.7015330426P09 WW WWOX-v1 Mm.33369 Hs.519 1.314 1.328 1.215 0.698 0.604 0.881 0.456 0.443 3.543 5.33 4.263 1.589 2.176 1.43 1.576 1.186 1.478 1.025 1.746 1.164 1.359 0.304 0.2329030416C10 WW WWOX-v2 Mm.33369 Hs.519 1.868 2.062 1.448 0.953 0.977 0.838 0.824 0.499 6.319 6.487 5.284 3.773 3.59 1.848 2.087 2.23 1.594 1.817 2.274 2.338 2.243 0.483 0.3872310058J06 WW TAZ Mm.227202 Hs.24341 1.509 1.816 1.327 1.15 1.213 1.338 0.794 0.769 1.062 1.849 0.974 1.209 1.344 1.734 0.792 1.882 0.997 1.213 1.236 0.837 0.811 0.845 0.4585430434O07 WW GAS7 Mm.40338 Hs.226133 1.617 1.23 0.909 0.521 0.619 1.4 0.235 0.489 0.745 0.816 0.59 0.918 1.2 1.446 0.593 1.114 0.885 0.837 0.707 1.824 1.42 1.05 0.8672310014F10 WW HYPB Mm.218959 Hs.6947 1.455 1.123 1.815 0.458 0.836 2.024 0.852 0.785 1.667 3.39 1.741 0.909 1.123 1.877 1.359 1.84 0.948 1.731 1.817 1.308 0.874 0.955 0.8141300010O06 WW WWP2 Mm.294777 Hs.315485 7 14.28 5.375 6.946 1.164 1.987 3.422 3.607 3.708 2.159 4.579 4.724 6.642 2.686 1.407 2.318 1.645 1.292 2.088 2.578 2.854 0.971 2.15

Page 24: New High-Throughput Mapping of a Dynamic Signaling Network in … · 2005. 3. 11. · Science Supporting Online Material Barios-Rodiles, p. 1 Science Supporting Online Material High-Throughput

4833419B05 MARCKS HCN1 Mm.131973 Hs.353176 1.168 0.728 1.079 0.616 1.165 0.982 1.825 0.926 1.035 1.028 0.958 1.342 1.197 1.045 1.519 1.02 1.217 0.812 0.456 2.168 1.97 1.209 0.981C430047J18 MARCKS NOLA1 Mm.24873 Hs.69851 0.723 0.826 1.085 0.559 0.525 1.36 2.173 1.491 0.91 1.225 0.877 1.325 1.084 1.009 1.003 0.942 1.1 1.05 0.85 4.474 5.098 3.818 1.164930523M17 MARCKS EIF4G3 Mm.268903 Hs.402697 1.211 0.709 0.828 0.574 0.371 0.778 1.224 1.03 0.561 0.626 0.958 1.153 0.944 0.964 0.756 0.849 1.025 0.706 1.03 1.084 1.201 2.116 0.7564833436C19 MARCKS KRT1 Mm.183137 Hs.80828 1.062 1.235 1.086 0.559 1.106 1.1 0.34 0.483 0.859 1.762 0.858 0.963 1.134 2.907 0.785 1.857 1.78 1.097 2.812 1.591 0.682 0.96 0.1060610011M24 MARCKS DP1L1 Mm.28147 Hs.76277 0.341 0.933 0.375 0.185 0.285 0.984 0.549 0.52 0.695 0.576 0.724 0.89 0.999 0.976 0.459 1.169 0.908 0.688 0.407 0.958 1.038 1.068 0.2933300001N19 MARCKS KRT10 Mm.22662 Hs.99936 1.584 0.708 1.025 0.333 0.271 1.986 0.578 0.353 0.868 0.681 0.633 0.957 1.052 0.819 0.841 0.942 0.979 0.748 1.376 1.417 1.906 1.091 1.0012410014M22 MARCKS MLP Mm.2769 Hs.75061 1.647 1.053 2.454 0.739 0.554 1.495 1.258 0.639 0.692 0.484 0.462 1.291 1.672 0.823 0.82 0.871 0.705 0.807 0.724 1.797 1.565 2.266 0.7362310014E01 MARCKS SFRS16 Mm.296949 Hs.43543 1.737 2.028 1.733 3.599 0.502 1.524 1.194 0.884 0.784 0.899 0.835 1.658 2.38 0.976 1.386 1.157 0.966 1.02 0.839 0.844 2.553 1.146 0.656NM_005900 MH1/MH2 SMAD1 Mm.223717 Hs.388294 0.577 0.687 0.394 0.456 12.3 2.601 1.84 0.799 1.098 0.621 0.532 0.873 1.776 1.458 0.729 1.181 0.749 1.556 1.502 1.248 1.751 2.12 9.896NM_005901 MH1/MH2 SMAD2 Mm.152699 Hs.110741 0.997 3.668 0.804 7.478 1.689 28.35 1.28 1.08 1.535 1.103 0.482 1.582 1.064 1.784 0.912 1.448 0.888 1.321 0.392 1.002 0.92 1.5 3.786NM_005902 MH1/MH2 SMAD3 Mm.7320 Hs.288261 1.247 4.96 0.417 8.201 4.132 21.39 0.517 0.584 0.552 0.77 0.576 2.559 6.976 1.253 0.626 0.937 1.255 1.185 0.299 1.047 3.25 14.48 16.91U58993 MH1/MH2 SMAD5 Mm.272920 Hs.167700 0.957 0.606 0.279 0.388 0.642 0.99 1.637 1.525 0.574 0.995 1.144 1.117 0.842 1.006 0.504 1.237 1.096 1.059 0.353 0.955 0.896 1.233 1.87AF035528 MH1/MH2 SMAD6 Mm.27935 Hs.153863 0.845 0.909 0.603 1.213 1.524 0.484 2.128 1.266 0.746 1.069 1.185 1.034 1.338 2.71 0.902 1.768 1.594 1.477 4.312 2.576 3.971 13.22 31.28NM_008543 MH1/MH2 SMAD7 Mm.34407 Hs.370849 1.337 1.156 0.895 0.412 1.093 1.475 1.195 0.594 2.042 1.629 3.392 1.328 1.185 2.177 1.435 1.884 1.611 1.387 5.244 2.188 3.074 7.684 57.252210402M20 SH2 FLJ20967 Mm.40974 Hs.17433 1.175 0.795 0.735 1.046 0.823 0.831 0.479 0.496 0.936 1.141 1.285 1.863 1.306 0.892 2.164 0.88 1.08 0.909 1.243 1.456 1.598 1.188 0.7842900029A15 SH2 MATK Mm.2918 Hs.437808 1.838 1.838 0.857 1.237 0.723 0.956 0.168 0.278 1.295 1.28 2.165 1.983 1.58 0.998 0.865 1.246 1.889 1.254 2.333 1.977 2.321 1.192 1.2215830401B18 SH2 SOCS4 Mm.91920 Hs.44439 1.005 1.629 1.212 1.706 0.951 1.132 1.354 0.856 2.196 4.284 4.455 1.592 2.105 3.512 2.441 2.06 2.173 4.015 3.162 1.946 1.763 2.878 6.9539030611B09 SH2 STAT1 Mm.277406 Hs.21486 2.746 1.904 1.403 1.916 3.385 3.428 0.702 0.908 1.966 2.453 4.119 2.15 2.457 2.46 3.983 2.039 1.823 2.453 1.794 1.981 3.143 2.544 2.486A930009E21 SH2 SLA2 Mm.31910 Hs.334489 1.201 0.948 0.872 0.442 0.589 1.247 0.611 0.833 1.176 1.759 2.537 1.395 1.312 1.202 0.755 1.197 1.572 1.096 1.083 1.311 1.448 3.13 2.5084933424C13 SH2 LOC284948 Mm.128597 Hs.209542 1.477 0.847 1.401 0.278 1.259 2.255 0.574 0.57 1.357 1.471 0.999 1.33 0.624 0.972 1.034 1.23 0.946 0.854 1.162 2.135 1.65 0.537 0.7922610014F08 SAM FLJ36175 Mm.288734 Hs.20848 1.06 0.956 0.977 0.275 0.894 1.26 0.536 0.481 0.842 1.066 0.847 1.405 0.769 1.064 0.632 0.892 1.057 0.872 0.547 1.866 1.725 0.585 0.5781110008G13 SAM PPFIA4 Mm.295105 Hs.153648 1.326 1.086 1.75 0.402 0.915 1.1 0.453 0.53 1.898 2.308 2.152 1.852 1.052 1.658 1.802 1.786 1.539 1.031 2.055 2.579 1.741 0.731 0.6822010107E08 SAM EPHA1 Mm.250517 Hs.89839 0.736 0.491 0.169 0.489 0.49 0.628 1.581 1.451 0.871 1.618 1.406 1.233 0.845 1.029 0.684 0.87 1.013 1.275 1.787 1.127 0.618 3.017 0.498030473B06 SAM ETV6 Mm.269995 Hs.171262 1.187 1.217 0.521 1.051 1.552 0.953 1.367 1.616 1.143 1.901 0.981 1.789 1.285 1.176 0.734 0.927 1.2 1.383 1.565 3.397 1.592 2.267 0.4181700021J16 SAM SAMD8 Mm.236484 Hs.282105 0.658 0.926 0.419 0.658 0.763 0.681 0.392 0.357 3.698 3.909 2.563 1.099 0.975 0.906 1.396 2.009 2.742 1.524 1.383 1.641 1.354 1.07 0.1892610002F09 FKBP FKBP4 Mm.12758 Hs.848 0.779 1.679 1.078 1.506 1.406 1.139 0.829 0.516 0.741 1.816 1.341 1.149 1.693 3.822 1.33 1.782 1.158 1.865 2.255 1.35 1.078 0.634 9.1842700038N19 FKBP FKBP3 Mm.28480 Hs.379557 1.341 0.854 0.578 0.574 0.558 0.71 0.49 0.722 0.45 0.65 0.582 1.098 0.995 0.809 0.605 0.912 0.893 0.719 0.356 1.453 1.736 1.853 1.5031110002O23 FKBP FKBP11 Mm.30729 Hs.438695 0.839 0.874 0.528 0.726 0.453 0.379 0.28 0.323 1.337 1.25 1.672 1.443 1.15 1.281 0.715 1.177 2.355 1.722 1.616 1.426 1.045 0.921 1.2771500011D07 FKBP FKBP1B Mm.20453 Hs.407482 1.064 0.671 0.278 0.563 0.319 0.555 0.617 0.574 86.52 45.98 113.2 1.508 1.206 2.484 1.455 1.081 16.37 13.26 4.293 1.155 1.015 1.465 1.8870610037L19 FKBP FKBP1A Mm.278458 Hs.374638 1.139 0.807 0.965 0.462 0.45 0.622 0.551 0.709 46.28 19.84 77.17 1.336 1.031 1.837 1.25 1.88 4.206 6.174 1.954 1.427 0.934 0.914 1.636NM_004799 Miscellaneous SARA Mm.150197 Hs.162051 2.376 0.741 0.972 1.225 0.557 1.225 0.939 1.224 0.423 0.637 0.761 1.255 0.88 1.066 1.104 1.017 1.613 1.043 1.66 1.075 0.818 0.872 0.615AF069303 Miscellaneous FOXH1 Mm.42011 Hs.159251 1.563 0.844 0.473 0.689 0.71 1.409 0.792 0.727 0.418 1.36 0.677 0.923 0.898 1.136 0.817 1.015 1.64 0.81 0.283 1.241 1.277 0.816 2.782Y13149 Miscellaneous GSC Mm.129 Hs.440438 4.954 3.163 2.639 8.476 0.537 0.634 0.489 0.579 1.058 0.987 1.841 3.446 2.105 1.336 1.56 1.84 1.366 1.522 1.238 1.089 1.698 1.328 1.4630610039E12 miscellaneous IRF7 Mm.3233 Hs.166120 2.892 2.26 1.075 2.163 1.784 2.175 0.344 0.81 2.347 3.047 3.16 2.53 2.426 1.541 1.956 2.124 3.477 2.445 3.377 1.588 1.722 1.817 1.643110001G18 miscellaneous IRF3 Mm.3960 Hs.75254 0.322 1.153 0.908 0.98 1.459 1.67 0.512 0.393 0.579 0.751 0.662 1.171 1.533 1.867 0.796 1.195 1.151 1.819 1.267 1.184 0.973 4.519 4.0129030603A05 miscellaneous ICSBP1 Mm.249937 Hs.14453 1.455 2.319 0.572 1.935 1.138 0.801 0.831 0.695 1.032 1.317 1.169 2.324 1.791 2.136 1.076 1.395 1.528 1.757 2.476 1.444 1.274 0.939 4.7622310004H24 Miscellaneous MEF2C Mm.24001 Hs.368950 1.007 1.52 0.792 0.501 0.426 1.232 0.736 0.773 0.611 0.908 0.701 1.153 0.61 0.928 0.648 1 0.7 0.7 0.572 2.567 1.071 0.857 2.222010013E14 Miscellaneous FLJ38819 Mm.23165 Hs.115959 0.799 0.767 1.39 0.331 1.384 1.859 0.754 0.83 1.295 2.188 0.968 1.398 0.647 1.443 0.902 1.248 1.117 1.284 2.441 1.985 1.489 0.705 0.4573110030A04 miscellaneous CED-6 Mm.133132 Hs.107056 0.596 0.782 0.741 0.208 1.445 0.961 0.8 0.724 1.243 1.893 1.237 1.362 0.591 1.132 0.874 1.426 1.327 1.132 1.237 2.29 1.082 0.045 0.7070610007A18 Miscellaneous SFRS5 Mm.43331 Hs.166975 2.012 1.599 2.141 0.568 1.694 1.075 0.635 0.717 1.992 2.089 2.722 1.57 0.794 1.001 0.978 1.386 1.268 1.615 2.216 16.81 12.2 0.982 1.0840610011A23 Miscellaneous ARHGDIB Mm.2241 Hs.292738 1.728 0.949 2.037 0.323 1.438 1.974 0.901 0.942 1.146 1.135 1.43 1.703 0.894 1.449 1.261 1.554 1.071 1.201 1.106 1.477 1.858 1.26 0.8332310004J15 Miscellaneous EFNA1 Mm.15675 Hs.399713 0.929 0.638 0.97 0.26 1.313 1.503 0.753 0.851 4.026 4.469 3.624 1.863 1.024 1.234 1.364 1.786 1.815 1.766 1.28 2.781 1.624 0.647 0.6472410003E11 Miscellaneous TXNL2 Mm.267692 Hs.42644 1.262 0.937 1.456 0.34 1.643 1.257 0.958 1.155 0.769 1.38 0.998 1.789 0.973 1.534 0.89 1.469 1.133 1.273 1.234 1.594 1.516 0.658 0.8222010007O02 Miscellaneous LENG8 Mm.22831 Hs.380446 1.057 0.94 1.376 0.266 1.318 1.145 1.407 1.873 1.152 1.769 1.26 1.72 0.766 1.841 0.888 1.425 1.147 1.694 1.051 2.3 1.258 0.342 0.6851810005H01 Miscellaneous SFRS4 Mm.2478 Hs.76122 0.399 0.914 0.324 0.644 0.6 0.907 0.375 0.388 0.453 0.69 0.444 1.166 0.759 0.827 0.498 0.579 0.576 0.699 0.358 7.031 8.111 3.551 0.7260610041G12 miscellaneous DIABLO Mm.46716 Hs.169611 0.925 0.686 0.28 0.647 0.85 1.282 0.965 0.957 2.665 2.948 2.16 1.313 0.96 1.013 0.935 0.729 1.07 1.23 0.834 1.791 1.427 2.98 0.5916330408J11 miscellaneous CGN Mm.87634 Hs.18376 1.625 1.582 0.93 1.093 1.436 0.928 0.868 1.172 0.829 1.305 0.608 0.967 0.976 0.848 0.624 1.152 1.056 1.204 1.188 1.628 1.877 1.844 0.4354921513I03 Miscellaneous CRB1 Mm.158473 Hs.444511 1.428 0.882 1.024 0.779 1.974 1.613 1.136 1.003 1.782 2.164 1.408 1.233 1.182 1.282 1.432 1.363 1.26 1.462 0.984 1.106 1.466 1.973 0.4474921514D13 miscellaneous DAP3 Mm.29028 Hs.270920 1.098 1.027 0.673 0.676 1.435 1.252 0.682 1.11 1.567 2.466 1.389 1.249 1.04 1.294 1.4 1.481 1.343 1.18 1.152 1.505 1.641 1.525 0.4391300002E07 Miscellaneous RHPN2 Mm.286600 Hs.335798 1.368 2.397 0.93 1.063 0.976 0.93 0.148 0.55 3.196 3.758 2.798 1.331 1.48 1.237 1.622 1.46 1.346 1.339 1.87 2.261 3.514 0.756 0.2633200001L20 Miscellaneous RTKN Mm.4139 Hs.58215 1.128 1.781 0.607 1.122 1.052 0.196 1.098 1.032 1.685 3.609 1.466 1.306 1.116 1.719 2.005 1.772 1.758 1.817 1.758 1.552 3.041 0.825 0.4221500041M20 miscellaneous CDC42EP4 Mm.293378 Hs.3903 0.912 1.043 0.618 1.453 1.723 0.5 1.009 1.255 1.313 3.009 1.64 1.703 1.519 1.638 1.736 1.302 1.817 1.951 1.566 1.969 1.575 1.976 0.7042610011H01 miscellaneous STX8 Mm.3973 Hs.380938 1.624 1.135 0.781 1.174 2.897 2.158 1.483 1.342 2.946 5.251 3.907 2.302 1.875 1.525 4.346 1.31 1.559 2.411 0.846 1.768 2.172 2.1 0.5562810018B18 miscellaneous 2810018B18 Mm.305491 1.075 1.306 0.759 0.993 1.487 0.818 0.755 0.849 6.193 3.798 4.042 1.331 1.144 3.357 4.894 4.941 2.282 2.798 2.689 1.085 1.708 1.935 0.332810455B10 miscellaneous ALS2CR19-v2 Mm.35593 Hs.26981 0.758 0.876 0.477 0.357 1.788 0.731 1.011 0.965 0.805 1.129 1.096 1.08 0.949 1.277 0.89 1.099 1.069 1.016 0.817 1.477 1.805 1.519 0.7483322402E17 Miscellaneous KIAA0290 Mm.22025 Hs.96485 1.305 1.512 0.92 1.239 2.047 1.193 1.302 1.133 1.669 2.982 1.549 1.304 2.133 1.976 3.588 1.874 2.03 1.878 2.196 2.802 3.749 0.941 0.6941300010N03 Miscellaneous UBTF Mm.2845 Hs.89781 0.922 0.64 0.289 0.358 0.546 0.526 0.784 0.766 0.883 1.386 1.401 1.1 0.841 1.214 0.698 1.365 1.197 1.183 1.489 3.918 2.3 1.347 0.6111700056A21 miscellaneous AVEN Mm.292041 Hs.63168 1.873 2.293 0.883 2.013 1.671 0.899 1.2 0.605 1.276 2.905 1.04 2.355 2.176 1.457 1.093 1.142 1.404 1.33 1.563 3.092 1.551 1.979 0.5015430439E07 Miscellaneous TP73 Mm.103715 Hs.192132 1.21 1.226 0.685 0.776 1.531 1.361 0.906 1.111 0.746 1.906 0.654 1.6 1.635 1.195 0.871 0.828 0.927 0.956 0.972 1.492 1.736 2.373 0.7042310003I18 miscellaneous ASH2L Mm.27706 Hs.6856 1.387 1.789 1.157 1.509 2.476 1.254 1.133 1.107 1.14 3.833 1.5 1.738 1.632 1.021 1.512 0.941 1.355 1.498 1.203 4.179 3.512 5.426 0.3865830472M02 Miscellaneous C20orf121 Mm.89828 Hs.283869 1.414 1.161 0.802 0.674 2.448 1.04 1.835 1.498 1.71 3.929 1.416 1.182 1.38 1.408 1.404 1.51 1.409 1.917 2.775 1.699 2.68 1.325 0.7762610529M21 Miscellaneous EFNA4 Mm.16332 Hs.449913 1.006 0.963 0.518 0.423 0.964 1.006 0.854 1.074 1.742 2.309 1.344 1.151 1.078 1.032 0.846 1.16 1.173 0.877 2.272 1.168 0.622 1.261 0.3223010029E15 Miscellaneous RGS19 Mm.274366 Hs.422336 1.33 1.03 0.584 0.698 1.697 0.895 2.082 2.027 1.27 3.56 2.025 1.387 1.233 1.149 1.561 1.639 1.237 1.428 1.825 1.447 2.173 0.956 0.867E130111N18 Miscellaneous RRH Mm.3917 Hs.158338 0.661 0.844 0.4 0.53 1.166 0.881 0.603 0.589 29.8 20.22 26.48 1.507 1.007 1.425 1.17 1.408 1.792 1.518 1.112 1.103 0.986 1.607 0.2455031426K15 Miscellaneous OCLN Mm.4807 Hs.171952 1.476 1.262 0.858 1.111 3.94 1.14 1.074 0.832 10.92 12 12.84 1.345 1.27 1.708 2.674 2.394 1.568 2.035 2.338 2.338 3.287 0.855 0.3885730571J11 miscellaneous HDGF Mm.292208 Hs.89525 1.847 1.837 0.776 0.746 3.39 0.853 1.156 1.579 0.632 0.839 0.543 1.421 1.999 0.885 0.721 1.35 0.676 0.561 0.602 2.433 2.271 1.4 1.2774632410H03 miscellaneous HDGFRP3 Mm.28887 Hs.127842 1.129 1.43 1.071 0.829 2.284 0.939 1.069 1.13 1.052 1.123 0.609 1.157 1.235 0.911 0.74 1.02 0.93 0.966 1.034 5.943 5.205 3.092 1.6891200002O22 miscellaneous NUMB Mm.4390 Hs.445301 2.363 1.4 1.337 1.294 2.01 2.492 1.147 0.545 1.237 0.906 1.774 1.396 1.741 0.881 1.019 0.916 1.058 0.86 1.395 2.235 2.731 1.623 1.1211700003H06 miscellaneous DAB1 Mm.289682 Hs.333942 0.882 0.945 0.557 0.579 1.04 2.395 1.179 0.891 0.727 0.775 0.504 1.219 1.268 0.804 0.87 0.777 0.755 0.671 0.793 2.704 2.525 1.668 1.0682900010F03 Miscellaneous GUK1 Mm.3624 Hs.376933 1.141 0.822 0.508 0.469 0.892 1.419 1.436 0.966 0.645 0.653 0.739 1.387 1.154 0.793 1.041 0.736 0.601 0.572 0.627 1.426 1.75 1.848 1.3091200015I07 miscellaneous APBB2 Mm.5159 Hs.324125 2.404 1.862 1.578 1.315 2.694 3.523 1.223 1.091 1.156 1.736 1.466 1.036 1.883 1.611 1.313 1.643 1.415 1.212 1.498 2.311 3.423 1.311 1.547AF022795 miscellaneous TGFBRAP1 Mm.246069 Hs.446350 1.409 1.235 0.224 0.718 2.072 2.054 0.751 0.722 1.562 1.033 0.681 1.412 1.034 1.069 0.871 1.448 1.197 1.037 1.216 1.77 1.971 0.613 0.091NM_001343 Miscellaneous DAB2 Mm.240830 Hs.81988 0.986 0.76 1.334 0.66 0.633 0.865 0.67 0.603 0.592 0.548 0.518 1.017 1.173 1.128 0.977 1.131 1.205 0.898 1.09 1.16 0.823 0.768 0.64X97674 Miscellaneous NCOA2 Mm.2537 Hs.446678 0.78 1.269 1.123 0.817 0.916 0.361 1.73 0.46 0.699 1.438 0.58 1.244 1.225 1.295 1.151 1.166 1.451 0.943 1.061 2.281 1.767 1.894 0.857AF175574 Miscellaneous PSMD4 Mm.2261 Hs.505059 1.025 1.043 0.342 0.732 1.562 0.867 1.214 0.68 2.995 1.869 2.196 1.275 1.171 1.577 1.374 1.309 1.746 1.331 1.305 1.418 2.408 0.527 0.077NM_012029 miscellaneous SITPEC Mm.271672 Hs.22199 0.733 1.628 0.982 0.486 0.819 0.292 0.79 0.451 2.692 1.5 1.503 1.099 1.203 1.35 0.963 1.463 1.408 1.494 1.345 3.547 2.455 0.764 0.317

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Table S3. False negative rate assessment for the TGFβ LUMIER datasetThe list of prey/bait combinations are previously known interactions

PREY BAIT/SCREEN LIR>3 LIR>2 LIR>11 SMURF2 WT SMAD2+TGFβ Y Y Y2 SMURF2 WT SMAD3+ TGFβ Y Y Y3 SMURF2 WT SMAD7 N N N4 SMURF2 WT SMAD1 Y Y Y5 SMURF2 WT SMAD1+BMP Y Y Y6 SMURF2(C716A) SMAD2+TGFβ Y Y Y7 SMURF2(C716A) SMAD3+ TGFβ Y Y Y8 SMURF2(C716A) SMAD7 Y Y Y9 SMURF2(C716A) SMAD7+TGFβ Y Y Y10 SMURF2(C716A) SMAD1 Y Y Y11 SMURF2(C716A) SMAD1+BMP Y Y Y12 SMURF1 WT SMAD7 N N N13 SMURF1(C699A) SMAD7 N N N14 SMURF1(C699A) SMAD7+TGFβ N N N15 SMURF1(C699A) SMAD1 Y Y Y16 SMURF1(C699A) SMAD1+BMP Y Y Y17 SMAD1 SMAD4 Y Y Y18 SMAD1 SMURF1(C699A) N N Y19 SMAD1 SMURF2 WT N Y Y20 SMAD1 SMURF2(C716A) Y Y Y21 SMAD2 SMAD2+TGFβ Y Y Y22 SMAD2 SMAD3+ TGFβ Y Y Y23 SMAD2 SMAD4+ TGFβ Y Y Y24 SMAD3 SMAD2+TGFβ Y Y Y25 SMAD3 SMAD3+ TGFβ Y Y Y26 SMAD3 SMAD4+ TGFβ Y Y Y27 SMAD5 SMURF1(C699A) N N N28 SMAD6 ACVR1(Q207D) N N Y29 SMAD6 BMPR1B(Q203D) Y Y Y30 SMAD6 SMURF1 WT N Y Y31 SMAD6 SMURF1(C699A) Y Y Y32 SMAD6 SMURF2 WT Y Y Y33 SMAD6 SMURF2(C716A) Y Y Y34 SMAD7 TGFβR1(T204D) Y Y Y35 SMAD7 ACVR1(Q207D) N N Y36 SMAD7 BMPR1B(Q203D) Y Y Y37 SMAD7 SMURF1 WT N Y Y38 SMAD7 SMURF1(C699A) Y Y Y39 SMAD7 SMURF2 WT Y Y Y40 SMAD7 SMURF2(C716A) Y Y Y41 SQSTM1 SMURF1 WT Y Y Y42 SQSTM1 SMURF1(C699A) Y Y Y43 MAP2K3 SMAD7 N N Y44 CAMK2D SMAD4 Y Y Y

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45 TGFβR1 TGFβR1 WT Y Y Y46 TGFβR1 TGFβR1(K232R) Y Y Y47 TGFβR1 TGFβR1(T204D) Y Y Y48 TGFβR1 ACVR1 WT Y Y Y49 TGFβR1 ACVR1(K235R) Y Y Y50 TGFβR1 ACVR1(Q207D) Y Y Y51 BMPRII TGFβR1 WT Y Y Y52 BMPRII TGFβR1(K232R) Y Y Y53 BMPRII TGFβR1(T204D) Y Y Y54 MAP3K7 SMAD7 N N N55 FKBP1A TGFβR1 WT Y Y Y56 FKBP1A TGFβR1(K232R) Y Y Y57 FKBP1A TGFβR1(T204D) Y Y Y58 FKBP1A BMPR1B WT Y Y Y59 FKBP1A BMPR1B(K231R) Y Y Y60 FKBP1A BMPR1B(Q203D) N N Y61 FKBP1B TGFβR1 WT Y Y Y62 FKBP1B TGFβR1(K232R) Y Y Y63 FKBP1B TGFβR1(T204D) Y Y Y64 FKBP1B BMPR1B WT Y Y Y65 FOXH1 SMAD2+TGFβ N N N66 FOXH1 SMAD3+TGFβ N N N67 SARA SMAD2 N Y Y68 SARA SMAD3 N N N69 IRF7 SMAD3 N N Y70 IRF7 SMAD3+ TGFβ N Y Y71 IRF7 SMAD4 N N Y72 IRF3 SMAD4 N N Y73 MEF2C SMAD3+ TGFβ N N N74 TGFBRAP SMAD4+ TGFβ N Y Y75 SITPEC SMAD4 N N N76 SITPEC SMAD1+BMP N N Y77 SKI SMAD2 Y Y Y78 SKI SMAD3 Y Y Y79 SKI SMAD4 Y Y Y80 UNRIP TGFβR1 WT N N N81 UNRIP TGFβR1(K232R) N N Y82 UNRIP TGFβR1(T204D) N N N83 UNRIP SMAD7 N N N

FALSE NEGATIVE RATE 30/83=36% 24/83=29% 14/83=17%

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Table S4. Interactions from TGFβ LUMIER with a LIR equal or greater than 3

BAIT/SCREEN Number of InteractionshRL-SMAD2 27hRL-SMAD2+TGFβ signal 33hRL-SMAD3 4hRL-SMAD3+TGFβ signal 21SMAD4-RL 50SMAD4-RL+TGFβ signal 24mSMAD7-hRL 2mSMAD7-hRL+TGFβ signal 3TGFβRI-RL WT 79TGFβRI-RL(K232R) 134TGFβRI-RL(T204D) 103hRL-SMAD1 47hRL-SMAD1+BMP signal 48ACVR1-hRL WT 23ACVR1-hRL(K235R) 43ACVR1-hRL(Q207D) 11BMPR1B-hRL WT 25BMPR1B-hRL(K231R) 40BMPR1B-hRL(Q203D) 48hRL-SMURF1 WT 56hRL-SMURF1(C699A) 83hRL-SMURF2 WT 19hRL-SMURF2(C716A) 24Total Number of Interactions 947