Handbook oCell Signaling

Volume 3

Ralph A. Bradshaw

Edward A. Dennis

VOLUME 3 Global Mechanisms of PIC Function:~-

Gene-Specific Regulation of PIC Function by

contributors

xlv

Transcriptional Activator sConclusion

PARTIII

References

NUCLEAR AND CYTOPLASMIC

CHAPTER 272

EVENTS: TRANSCRIPTIONAL AND Structural Mechanisms of Ligand-Mediated

POST TRANSCRIPTIONAL

Signaling by Nuclear Receptors

21H. Eric Xu and Millard H . Lambert

REGULATIONMichael Karin, Editor

Introductio nOverall Structure of the LB DLigand-Binding Pockets

PART III

Ligand-Mediated Activation : Mouse Trap versu sIntroduction

Charged Clamp

Michael Karin

Ligand-Mediated RepressionDimerizatio n

Section A: Nuclear Receptors

Summary

Michael G . Rosenfeld, Editor

Reference s

CHAPTER 270.

CHAPTER 273

History of Nuclear Receptors

7 Nuclear Receptor Coactivators

25Elwood V. Jensen

Riki Kurokawa and Christopher K . Glass

Introduction

Introduction

Discovery of Receptors and Shift in Research Direction,

Mechanism of Coactivator Recruitment

Receptor Forms and Physiological Action

General Classes of Coactivator Complexes

Subsequent Discoveries Relevant to Receptor

Coactivators as Targets of Signal Transduction Pathway s

Structure and Function

Conclusion

References

ReferencesS

CHAPTER 271

CHAPTER 274- .Regulation of Basal Transcription by

Corepressors in Mediating Repression b yRNA Polymerase II

11 Nuclear Receptors

29Sohail Malik and Robert G. Roeder

Kristen Jepsen and Michael G . Rosenfeld

Introduction

Introductio nThe Preinitiation Complex

N-CoR and SMRT in Repression by Nuclear Receptors

Purification of Corepressor Complexes

FXR: Bile Acid SensorOther Nuclear Receptor and Transcription Factor Partners

PXR and CAR: Xenobiotic Sensor sof N-CoR/SMRT

Ligands for Other Orphan Nuclear Receptor sMultiple Mechanisms of N-CoR/SMRT Regulation

Conclusio nRoles in Development and Disease

Reference sOther Mediators of Nuclear Receptor Repressio nConclusion

CHAPTER 279References

Orphan Receptor COUP-TFII an d

CHAPTER 275

Vascular Development

57Fabrice G. Petit, Sophia Y. Tsai, and Ming-Jer Tsa i

Steroid Hormone Receptor Signaling

35Vincent Giguere

Introductio n

Vascular DevelopmentIntroduction

PPARy: Inhibitor of Angiogenesi sActivation by the Hormone

COUP-TFII : Positive Effector in Angiogenesi sHormone-Independent Activation

Conclusio nCross-Talk with Other Transcription Factors

Reference sNongenomic Action of Steroid Hormone sEstrogen Related Receptors

CHAPTER280Selective Steroid Hormone Receptor Modulator sReferences

Crosss-Talk between Nuclear Receptorsand Other Transcription Factors

61CHAPTER 276

Peter Herrlich

PPARy Signaling in Adipose Tissue

Introductio nDevelopment

39

Proliferation and Proinflammatory PathwaysRobert Walczak and Peter Tontonoz

Nuclear Receptor s

Introduction

Induced Expression of Inhibitory Molecule s

PPARy: A Dominant Regulator of Adipose Tissue

Immediate Hormone Responses

Development

Direct Modulation of Transcription Factor s

Analysis of PPARy Function in Animal Models

Conclusion

Transcriptional Networks in Adipose Tissue

Reference s

DevelopmentNegative Regulation of Adipocyte Differentiation

CHAPTER 281PPARy, TNF-a Signaling Antagonism and Insulin

Drosophila Nuclear Receptors

69Resistance

Kirst King-Jones and Carl S . ThummelPPARy and Cell Cycle Regulatio n

References

IntroductionNuclear Receptors and Embryonic Pattern Formatio n

CHAPTER 277

Ecdysone Regulatory Hierarchie s

The Neuronal ConnectionOrphan Nuclear Receptors

47 Reference sBarry Marc Forman

Classical Receptors versus Orphan Receptors

Section B: Transcription FactorsOrphan Receptors and Metabolite-Derived Signal sOrphan Receptors and Xenobiotic Signals

Marc Montiminy, Edito r

Future Direction sReferences

CHAPTER 282

CHAPTER 278

JAK-STAT Signaling

77Christian W. Schindler

Identification of Ligands for OrphanNuclear Receptors

53

Introduction

Steven A . Kliewer and Timothy M . Willson

The JAK STAY ParadigmThe JAK Family

Introduction

The STAT FamilyPPARs : Fatty Acid Sensors

A Promising FutureLXRs: Cholesterol Sensors

References

CHAPTER 283

CHAPTER 286FOXO Transcription Factors : Key

NF1 B : A Key Integrator of CellTargets of the PI3K-Akt Pathway That

Signaling

107Regulate Cell Proliferation, Survival, and

John K . Westwick, Klaus Schwamborn, and Frank Mercurio

Organismal Aging

83 ReferencesAnne Brunet, Hien Tran, and Michael E . Greenberg

Introduction

CHAPTER 287Identification of the FOXO Subfamily of

Transcriptional Regulation via the cAMPTranscription Factors

Responsive Activator CREB

115Regulation of FOXO Transcription Factors by the

Marc Montminy and Keyong D uPI3K-Akt Pathway

Other Regulatory Phosphorylation Sites in

The Transcriptional Response to cAMP

FOXOs

Mechanism of Transcriptional Activation

Mechanism of the Exclusion of FOXOs from

via CRE B

the Nucleus in Response to Growth Factor

Signal Discrimination via CRE B

Stimulation

Secondary Phosphorylation of CREB : Ser14 2

Transcriptional Activator Properties of

Methylation of the KIX Domain

FOXOs

Cooperative Binding with MLL

FOXOs and the Regulation of Apoptosis

Reference s

FOXOs Are Key Regulators of Several Phases o fthe Cell Cycle

CHAPTER288FOXOs in Cancer Development : Potential Tumor

The NFAT Family : Structure,Suppressors

Regulation, and Biological Functions

119Role of FOXOs in the Response to Stress and

Fernando Macian and Anjana Ra oOrganismal Aging

FOXOs and the Regulation of Metabolism in

Introductio n

Relation to Organismal Aging

Structure and DNA Bindin g

Conclusion

Regulation

References

Transcriptional FunctionsBiological Programs Regulated by NFAT

CHAPTER 284

PerspectivesReference s

Multiple Signaling Routes to Histon ePhosphorylation

91 CHAPTER 289Claudia Crosio and Paolo Sassone-Corsi

Transcriptional Control throughIntroduction

Regulated Nuclear Transport

125Histone Phosphorylation and Gene Activation

Steffan N . HoHistone Phosphorylation and DNA RepairHistone Phosphorylation and Apoptosis

Introductio nRegulated Nuclear Transport: Overview

Histone Phosphorylation and Mitosis

Coordinate Regulation of Nuclear Import and Export :Conclusions

Calcium-Dependent Nuclear Localization of NFAT cReferences

Transcription Factor sRegulated Nuclear Transport of Non-DNA-Binding

CHAPTER 285

Transcriptional Regulatory Proteins

Multigene Family of Transcription

Conclusion

Factor AP-1

99 Reference sPeter Angel

CHAPTER 290Introductio nGeneral Structure of AP -1 Subunits

Proteasome/Ubiquitination

129Transcriptional and Posttranslational Control of

Daniel Kornitzer and Aaron Ciechanove r

AP-1 Activity

Protein Degradation and the Ubiquitin/Proteasome SystemFunction of Mammalian AP-1 Subunits : Lessons from

Regulation of Ubiquitination by Substrate Modificatio nLoss-of-Function Approaches in Mice

Regulation of Ubiquitin Ligase ActivityReferences

Protein Processing by the Ubiquitin System

Modulation of Kinase Activity by Ubiquitination

CHAPTER 296Conclusion

Cubitus Interruptus

167References

Sarah M. Smolik and Robert A . Holmgren

CHAPTER 291

Introduction

Fluorescence Resonance Energy Transfer

Protein Structure and Expression Patterns of C i

Microscopy and Nuclear Signaling

135 Regulation of Ci by HedgehogTy C . Voss and Richard N . Day

Regulation of Ci by PKACi Transcriptional Regulation

Introduction

Reference sReferences

CHAPTER 297CHAPTER 292

The Smads

171The Mammalian Circadian

Malcolm Whitma n

Timing System

139Introduction

Ueli Schibler, Steven A. Brown, and Jürgen A. Ripperger

Families : RSmads, Co Smads, and I -Smads

Introduction

Smad Oligomerization and Regulation by Receptor s

The Molecular Oscillator

Transcriptional Regulation by Smad s

Photic Entrainment of the Central Pacemaker

Down-Regulation and Cross-Regulation of Smad s

Outputs of the SCN Pacemaker

Function In Vivo : Gain of Function Loss of Function

Outputs via Subsidiary Clocks

Reference s

Conclusions and Perspective sReferences

Section C: Damage/Stress Responses

CHAPTER 293

Albert J . Fornace, Jr ., Editor

Protein Arginine Methylation

145 CHAPTER 298Michael David

Complexity of Stress SignalingIntroduction

and Responses

179Arginine Methylation and Arginine-Methyltransferase sFunction of Arginine Methylation

Sally A . Amundson and Albert J . Fornace, Jr.

Role of Arginine Methylation in Signal Transduction

Introduction : A Variety of Stresses

References

Origin of SignalsSignal Transduction

CHAPTER 294

Functional Genomics and Proteomics Approache s

Transcriptional Activity of Notch and

References

CSL Proteins

149CHAPTER 299

Elise Lamar and Chris KintnerSignal Transduction in the

Introduction

Escherichia coli SOS Response

185Components of the Notch Transcriptional Comple x

Notch Transcriptional Activity In Vivo

Penny J . Beuning and Graham C . Walker

Conclusion

SOS Respons e

References

LexA Cleavage and Other Self-Cleavage Reaction sRegulating the SOS Response

CHAPTER 295

Structures of Y-Family Polymerases

The ß-Catenin: LEF/TCF Signaling

Conclusion s

Complex: Bigger and Busier than Before 161 Reference sReiko Landry and Katherine A. Jones

CHAPTER300Introduction

Oxidative Stress and Free Radical Signa lRegulated Proteolytic Turnover of 13-Cat

Transduction

191Regulation of the Wnt-Assembled Enhancer Complex

Bruce Demplein the Nucleus

Enter Pygopus and Legless (hBc19)

Introduction : Redox Biolog y

Perspectives

Oxidative Stress Responses in Bacteria : Well-Define d

References

Models of Redox Signal Transduction

Responses to Superoxide Stress and Nitric Oxide :

Introductio nSoxR Protein

Repair of DSBs : Homologous Recombination and NHEJResponse to H202 and Nitrosothiols : OxyR Protein

Recognition of DNA DSBsParallels in Redox and Free-Radical Sensing

Signal TransductionThemes in Redox Sensing

DNA Repai rReferences

Other Sensors and Transducers of DNA DamageNew Factors in NHE J

CHAPTER 301

Future Prospects

Budding Yeast DNA Damage Checkpoint :

Reference s

A Signal Transduction-MediatedSurveillance System

197 CHAPTER 305Marco Muzi-Falconi, Michel Giannattasio, Giordano Liberi,

Role of ATM in Radiation Signa lAchille Pelliccioli, Paolo Plevani, and Marco Foiani

Transduction

225Introduction

Martin F. Lavin, Shaun Scott, Philip Chen, Sergei Kozlov ,

Sensing

Nuri Gueven, and Geoff Birrel l

Downstream Events

Introductio nReferences

Sensing Radiation Damage in DNAATM Signaling : Recognition of Breaks in DNA

CHAPTER 302

Checkpoint Activation

Finding Genes That Affect Signaling and

Role of ATM in More General Signaling

Toleration of DNA Damage, Especially

Perspective

DNA Double-Strand Breaks

203Reference s

Craig B . Bennet and Michael A . Resnick CHAPTER 306Introduction

Signaling to the p53 Tumor SuppressorNature of DSB and Repair and Genetic Consequences

through Pathways Activated byCheckpoint Activation and Adaptation as Signaling

Responses to DSBs

Genotoxic and Nongenotoxic Stresses

237DNA Damage Signaling Networks

Carl W. Anderson and Ettore Appella

Identifying Checkpoint Defects by Screening Radiation-

IntroductionSensitive Mutants

p53 Protein StructureCheckpoint Mutants Revealed through Screening DNA

Posttransitional Modifications to p5 3Replication Mutants

Regulation of p53 ActivityScreening for Checkpoint Defects

Activation of p53 by Genotoxic Stresse sScreen for Altered Checkpoint and Adaptation Responses

Activation of p53 by Nongenotoxic Stresse sto a Single DSB

Conclusion sOther Screens for DNA Damage Checkpoint Pathway

Reference sGenes

Implications of DNA Damage Checkpoint Signaling

CHAPTER 307References

Abl in Cell Signaling

249CHAPTER 303

Jean Y. J . Wan g

Radiation Responses in Drosophila

213 IntroductionNaoko Sogame and John M . Abrams

Functional Domains of Ab lProteins that Interact with Abl

Introduction

Abl in Signal TransductionSensors and Transmitters

Future ProspectsEffectors

ReferencesConclusions : What Can We Learn from the

Drosophila Model?

CHAPTER308References

Radiation-Induced CytoplasmicCHAPTER 304

Signaling

257Double-Strand Break Recognition and Its

Christine Blattner and Peter Herrlich

Repair by Nonhomologous End Joining 219 IntroductionJane M . Bradbury and Stephen P. Jackson

Cytoplasmic Signaling Network

Redox Sensitivity and Metal Toxicity : Toxic Agents

Conclusion sActivate Signaling Pathways

Reference sActivation of Signaling Component sPrimary Radiation Targets : DNA Damage versu s

Cytoplasmic Signaling

Section D: Post-Translational Contro lOther Signaling-Initiating Principles

Nahum Sonenberg, Edito rConclusion sReferences

CHAPTER 313CHAPTER 309

RNA Localization and Signal

Endoplasmic Reticulum Stress

Transduction

293

Responses

263

Vaughan Latham and Robert H . Singer

David Ron

IntroductionGrowth Factors Induce mRNA Localizatio n

IntroductionER Stress Defined

Signaling from the Extracellular Matrix Induces mRN A

The UPR in Yeast

Localization

The UPR Is Metazoans

mRNAs Localized via the Cytoskeleto n

Conclusions

mRNA Granule Movement in Neuron s

Ref

Regulation of mRNA Localizing Protein sReferences

GTPase Signals Regulating Actomyosin Interaction sAre Involved in mRNA Localization

CHAPTER 310

Conclusio n

The Heat-Shock Response : Sensing

Reference s

the Stress of Misfolded Proteins

269Richard I . Morimoto and Ellen A . A. Nollen

CHAPTER 314

Introduction

Translational Control by Amino AcidsTranscriptional Regulation of the Heat-Shock

and Energy

299Response

Tobia Schmelze, Jose L. Crespo, and Michael N. Hall

Molecular Chaperones : Folding, Misfolding, and the

IntroductionAssembly of Regulatory Complexes

GCN SystemNeurodegenerative Diseases : When Aggregation-Prone

TOR Signaling PathwayProteins Go Awry

Reference sReferences

CHAPTER 315CHAPTER 311

Translational Control and InsulinHypoxia-Mediated Signaling

Signaling

305Pathways

277

Thomas Radimerski and George Thoma sAlbert C . Koong and Amato J . Giaccia

ReferencesIntroductionHIF-1 Signaling

CHAPTER 316Unfolded Protein Response

Unfolded Protein Response : An IntracellularConclusions

Signaling Pathway Activated by th eReferences

Accumulation of Unfolded Proteins in th e

CHAPTER 312

Lumen of the Endoplasmic Reticulum

311Randal J. Kaufman

Regulation of mRNA Turnover b yCellular Stress

283

IntroductionCellularG tr

UPR in Saccharomyces cerevisiaeMyriam

UPR Transcriptional Activation in MetazoanIntroduction

SpeciesmRNA Stability

Physiological Role for the UPR in MammalsStress-Activated Signaling Molecules that Regulate

Future Direction smRNA Turnover

References

CHAPTER 317

Summary

Regulation of mRNA Turnover

319 Introduction

Perry J . Blackshear and Wi S . Lai

Members of the NF90 Protein FamilyDomain Structure of NF90 Family Proteins

Introduction

Proteins that Interact with NF9 0Current Models of mRNA Stability in Vertebrate Cells

Nucleic Acid Binding Properties of NF9 0Presence of Instability Elements in Vertebrate mRNAs

Functions of NF90 HomologsEffects of ARE Binding Proteins on mRNA Turnover

Cellular Regulation of NF90 and NF45Regulation of TTP Activity in Cells

ConclusionsConclusion

Reference sReferences

CHAPTER322CHAPTER 318

Signaling Pathways that Mediat eCPEB-Mediated Translation in Early

Translational Control of RibosomeVertebrate Development

323 Recruitment of mRNA

343Joel D . Richter

Nahum Sonenberg and Emmanuel Petroulaki s

Introduction

Introductio nMechanism of Translational Control

eIF4F Complex FormationCPEB and Early Development

Repressors of Cap-Dependent TranslationConclusions

Modulation of 4E-BP Phosphorylation FRAP/mTO RReferences

Phosphorylation of eIF4G and eIF4BControl of Cell Growth and Proliferation by

CHAPTER319

eIF4E : Link to Cancer

Translational Control in Invertebrate

Conclusion sReference s

Development

327Paul Lasko

Introduction

PARTIVTranslational Control Targets Oskar to the Pole

EVENTS IN INTRACELLULA RPlasm

COMPARTMENT STranslational Control Targets Nanos to the Pole

Plasm

Marilyn Farquhar, Editor

Translational Control in the Drosophila Nervous

CHAPTER 323SystemRole for Translational Control in Regulation

SREBPs: Gene Regulation throug hGrowth

Controlled Protein Trafficking

353Translational Repression through MicroRNAs

Peter J . Espenshade, Joseph L . Goldstein, and Michael S . Brow nReferences

Introduction

CHAPTER 320

SREBPs : Membrane-Bound Transcription Factor sSCAP: Sterol Sensor and Escorter of SREBP fro m

Role of Alternative Splicing During the

ER to Golg iCell Cycle and Programmed Cell Death 331 Sterols Control Sorting of SCAP/SREBP into ER Vesicle sChanseok Shin and James L . Manley

ER Retention of SCAP/SREB P

Introduction

Conclusions

Apoptosis and Splicing

References

Cell Cycle and Splicing RegulationReferences

CHAPTER 324Endoplasmic Reticulum Stres s

CHAPTER 321

Responses

359NF90 Family of Double-Stranded

David Ron

RNA-Binding Proteins : Regulators

Introductio nof Viral and Cellular Function

335 ConclusionTrevor W. Reichman and Michael B . Mathews

References

CHAPTER 325

CHAPTER 328Signaling Pathways from Mitochondria

Regulation of Cell Cycle Progression

40 1to the Nucleus

365 Clare H . McGowanZhengchang Liu and Ronald A . Butow

Introduction

Introduction

Being There: Cyclins Define Cell Cycle Phase

Milestones in Mitochondrial Research

Signals to Slow Processes : Regulation of Cdks by

Mitochondrial Signaling

Inhibitory Proteins

Aging and Retrograde Regulation

Cdks Are Positively and Negatively Regulated by

Conclusions

Phosphory I ation

References

Degradation : The Importance of Being Absen tLocation, Location, Locatio nCheckpoint Signaling

CHAPTER 326

Reference s

Signaling During Exocytosis

375Lee E . Eiden

CHAPTER 329Introduction

Endocytosis and Cytoskeleton

41 1Functional, Morphological, and Historical

Pier Paolo Di Fiore and Giorgio Scit a

Aspects of Exocytosis and Stimulus-Secretion

IntroductionCoupling

Actin Dynamics and Endocytosi sSecretion Begins with Secretagogues

Role of Microtubule Cytoskeleton in Receptor Endocytosi sSecretagogues Act at Target Cell

Physical and Functional Interactions of Dynamin andReceptors

Dynamin-Interacting Proteins with the ActinCalcium and Cyclic AMP : The Two Main Second

Cytoskeleto nMessengers for Secretion

Integration of Signals in Endocytosis and Actin DynamicsCalcium and the Regulation of Exocytosis

by Small GTPase sExocytosis and SNAREs

Conclusion sCalcium and cAMP Sensors for Exocytosis

Reference sRole of Signal Summation in Regulated

Exocytosis

CHAPTER 330Role of PKC and Other PMA Targets i nRegulated Secretion

Molecular Basis for Nucleocytoplasmi cNegative Regulation of Secretion

Transport

419Upstream Regulation of Secretion

Gino Cingolani and Larry Gerac eFar Upstream Regulation of SecretionConclusions and Future Outlook for Signaling in

Introduction

Exocytosis

Transport Signals

References

Transport Receptor sThe Small GTPase RanNuclear Pore Complex

CHAPTER 327

Mechanism of Transpor t

Nonclassical Pathways of Protein

Future Direction s

Export

393Reference s

Igor Prudovsky, Anna Mandinova, Cinzia Bagala,

CHAPTER 33 1Raffaella Soldi, Stephen Bellum, Chiara Battelli ,Irene Graziani, and Thomas Maciag

Apoptosis Signaling : A Means to an End 43 1

Introduction

Lisa J . Pagliari, Michael J . Pinkoski, and Douglas R . Green

Fibroblast Growth Factor Export Pathways

Introductio nThe Export of FGF-1 as a Multiprotein

The End of the Roa d

Complex

Caspase-8 Activation via Death Receptor sInterleukin-1 Export Pathways

Mitochondria and the Activation of Caspase- 9Acidic Phospholipids and the Molten Globule

Mitochondrial Outer Membrane Permeabilizatio nHypothesis

The Bcl-2 Famil yThe Potential Pathophysiological Implication of

Cell Cycle versus Apoptosis

Nonclassical Release

Conclusion s

References

References

CHAPTER 332

Myocardial Growth

Signaling Down the Endocytic Pathway 441 Cardiac Valve Formatio n

Jeffrey L . Benovic and James H. Keen

Cardiac Outflow Tract and Aortic Arch Developmen tConclusions

Introduction

ReferencesRTK Signaling from the Cell Surfac eRTK Signaling from Endocytic Compartments

CHAPTER 336GPCR Signaling Paradigms and Desensitization

Development and Regulatory Signalin gControl of RTK and GPCR Trafficking Leading t oDegradation

in the Pancreas

471GPCR Activation of MAP Kinases

Murray Kor c

Endocytic Signaling in Developmental Systems

IntroductionSignaling between Neuronal Cell Body and Terminal

Ontogeny of the PancreasReferences

Pancreatic Islet-Acinar Interaction sCell-Cell and Matrix Interactions in the Endocrine

PancreasPARTV

Matrix and Cell-Cell Interactions in the Exocrine Pancrea s

CELL-CELL AND CELL-MATRIX

Conclusion s

INTERACTIONS

Reference s

E. Brad Thompson, Editor

CHAPTER 337Tropic Effects of Gut Hormones in th e

PARTV

Gastrointestinal Tract

477Introduction

B . Mark Evers and Robert P. Thomas

Brad Thompson

IntroductionTropic Effects of Gut Peptides in the Stomach, Smal l

CHAPTER 333

Bowel, and ColonOverview of Cell-Cell and Cell-Matrix

GI Hormone Receptors and Signal Transduction Pathway s

Interactions

452

Signaling Pathways Mediating the Effects o f

E. Brad Thompson and Ralph A . Bradshaw

Intestinal Peptide sConclusions

References

References

CHAPTER 334

CHAPTER 338Angiogenesis : Cellular and Molecular

Integrated Response to NeurotrophicAspects of Postnatal Vessel Formation

455 Factors

485Carla Mouta, Lucy Liaw, and Thomas Maciag J. Regino Perez-Polo

Introduction

Introductio nInitiators of Angiogenesis : Cellular, Metabolic, and

Neural Cell DeathMechanical

The Neurotrophic Hypothesi sVessel-Specific Requirements in Angiogenesis

NeurotrophinsCellular and Soluble Regulators

Neurotrophin ReceptorsCoordination of Angiogenesis by Cellular and

Neurotrophin Signaling Pathway sMolecular Interactions

Transcriptional RegulationReferences

AP- 1

CHAPTER 335

NFKB Transcription FactorRole of NFKB

Signaling Pathways Involved

Conclusion sin Cardiogenesis

463 Reference sDeepak Srivastava

Introduction

CHAPTER 339Cardiomyocyte and Heart Tube Formation

Cell-Cell and Cell-MatrixCardiac Looping and Left-Right Asymmetry

Interactions in Bone

497Patterning of the Developing Heart Tube

L. F. Bonewald

Introduction

Coreceptor and Costimulatory Proteins ModulateDiseases of Bone

T-Cell Signaling Pathway sBone Cells and Their Functions

Intracellular Signaling Pathways Induced by Antige nMechanical Strain

Stimulation of T CellsHormone Responsible for Bone Development,

Conclusion sGrowth, and Maintenance

Reference sGrowth and Transcription Factors Responsible for Bon e

Development and Growth

CHAPTER 344Fibroblast Growth Factors

Signal Transduction via the B-Cel lBone Extracellular MatrixConclusions

Antigen Receptor: A Crucial Regulato rReferences

of B-Cell Biology

555Louis B . Justemen t

CHAPTER 340

IntroductionCell-to-Cell Interactions in Lung

509

Initiation of Signal Transduction through the BCRJoseph L . Alcorn

Propagation of Signal Transduction via the BCR

Introduction

Conclusions

Lung Organogenesis and Development

References

Soluble Factors of Cell-to-Cell Interactions Involved in

CHAPTER 345Lung InjuryConclusion

Signaling Pathways in the Normal andReferences

Neoplastic Breast

565Danica Ramljak and Robert B . Dickson

CHAPTER 341

IntroductionMechanisms of Stress Response Signaling

Signaling Molecules : A Class of Growth Factor sand Recovery in the Liver of Young versus

PI3K/Akt, MEK/Erk, and Stats : Major Proliferation/

Aged Mice : The p38 MAPK and SOCS

Survival Molecules Downstream of Growth Factor

Families of Regulatory Proteins

515

Receptors in Breas t

John Papaconstantinou

Conclusions and Future ProspectsReference s

IntroductionThe p38 MAPK Pathway in Stress Response

CHAPTER 346Signaling

Kidney

573SOCS Family of Negative Regulators of Inflammatory

Elsa Bello Reuss and William J . Arendshors tResponse

Conclusions

Overview of Kidney Functions and Cell-to-CellReferences

Interaction sVascular Endothelial Cell s

CHAPTER 342

Vascular Smooth Muscle Cells

Cell-Cell Signaling in the Testis and

Tubulovascular Interactions : The Juxtaglomerular Apparatu s

Ovary

531

Tubulovascular Interactions : The Juxtaglomerular

Michael K. Skinner

Apparatus and Tubuloglomerular Feedbac kVasculotubular Communicatio n

Introduction

Tubule-Tubule Communication : Paracrine Agent sCell-Cell Signaling in the Testis

Released from Epithelial Cell sCell-Cell Signaling in the Ovary

Interstitial Cell-Tubule CommunicationConclusions

Conclusion sReferences

Reference s

CHAPTER 343

CHAPTER 347T Lymphocytes

546 Prostate

591Rolf König and Wenhong Zhou

Jean Closset and Eric Reite r

Introduction

IntroductionSignaling Receptors in T Cells form Dynamic

Development of the Prostate during Fetal LifeMacromolecular Signaling Complexes

The Adult Prostate

The Prostate during AgingConclusion sReference s

CHAPTER 348Retrograde Signaling in the Nervou sSystem: Dorsal Root Reflexes

607William D . Willi s

Cell-to-Cell Signaling in the Nervous SystemRetrograde SignalingNeurogenic InflammationDorsal Root Reflexes as Retrograde SignalsConclusionsReferences

CHAPTER 349Cytokines and Cytokine Receptors Regulatin gCell Survival, Proliferation, andDifferentiation in Hematopoiesis

615Fiona J. Pixley and E. Richard Stanley

General Aspects of HematopoiesisSignaling through Cytokine Receptor sConclusionsReference s

CHAPTER 350Regulation of Bartlett Endogenous StemCells in the Adult Mammalian Brain :Promoting Neuronal Repair

625Rodney L. Rietze and Perry F. Bartlett

Adult Neurogenesis Reveale dIsolation and Culture of Neural Stem Cell sRegulation of Stem Cell Differentiation into Neuro nReferences

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