Functions of Onc-Gene Products:Growth Factor Receptors

Signal Transduction,Nuclear Transcription Factors

Folder Title: OncProteins

Updated: April 20, 2010

OncProtsTitle

How Weinberg’s Biology of Cancer Book is Set Up

Chapter 3: Oncogenic Viruses:

There are oncogenes.

Viruses Reveal Them

Chapter 4: Oncogenes

What these oncogenes are. How Many There Are.

Where they function

Chapters 5 and 6: Oncogene Products

How they contribute to the neoplastic phenotype

Chapter 5: Growth Factors, Growth Factor Receptors, Transmembrane Signal Transduction

Chapter 6: Cytoplasmic Signal Transduction to the Nucleus

Chapters 7, 8, 9: Tumor Suppressor Genes

Chapter 8: Retinoblastoma Protein and Cell Cycle Control

Chapter 9: p53 Tumor Suppressor Protein and Control of Apoptosis

Normal Cellular Functions for c-Onc-Gene Products (Part 1)(edited from Table 7-3, pp 288-9, Ruddon, 3rd Ed.)

...Shortened Version

Growth Factors• sis Platelet-derived GF viral transduction• int-2 Fibroblast GF-related viral insertion

Growth Factor Receptor, Tyrosine Kinase Activity• erbB Epidermal GF receptor (truncated) viral transduction• fms Colony-stimulating GF receptor (mutated) viral transduction• neu Receptor-like (unknown ligand) DNA transfaction• kit Stem-cell GF receptor (truncated) viral transduction

Non-receptor, Cytoplasmic Tyrosine-Kinase Activity• src Membrane-associated viral transduction• abl/bcr-abl viral transduction

cOncDo1

Normal Cellular Functions for c-Onc-Gene Products (Part 2)(editted from Table 7-3, pp 288-9, Ruddon, 3rd Ed.)

Cytoplasmic Serine-Kinase Activity• raf/mil viral transduction• mos viral transduction

Membrane Associated G Proteins• H-ras & GTP-binding GTPases viral transduction &

DNA K-ras transfection• N-ras GTP-binding GTPase DNA Transfection

Unclassified Cytoplasmic Proteins• bcl-2 Anti-apoptotic* Chromosome translocations

*Antiapoptotic = pro-cancer

cOncDo2

Normal Cellular Functions for c-Onc-Gene Products (Part 3)(editted from Table 7-3, pp 288-9, Ruddon, 3rd Ed.)

Nuclear Transcription Factors• myc DNA-binding Protein viral transduction• jun DNA-binding Protein viral transduction• myb DNA-binding Protein viral transduction

cOncDo3

Cell Surface Receptors

G-Protein (B)and Enzyme-linked (C)Classes of Cell-SurfaceReceptorsFig. 15-12Essential Cell Biologyp. 491, Alberts et al.

CellReceptors

Figure 5.12a The Biology of Cancer (© Garland Science 2007) p. 131

Mutations or Truncations of Receptor Leading to Misfiring

Figure 5.11 The Biology of Cancer (© Garland Science 2007) p. 130

Truncated Epidermal Growth Receptor in Avian Erythroblastosis

Table 5.2 The Biology of Cancer (© Garland Science 2007) p. 133

Figure 5.12b The Biology of Cancer (© Garland Science 2007) p. 131

Autocrine Stimulation

Figure 5.12c The Biology of Cancer (© Garland Science 2007) p. 131

Stained for Epidermal Growth Factor Receptor (EGF) (Red)

Stained for Transforming Growth Factor –alpha (a ligand for EGF receptor) (Green)

Yellow shows Red and Green Staining in the Same Cells

(Autocrine Stimulation Loop)

Autocrine Stimulation in Invasive Breast Carcinoma in

Humans

Please send in your name under “Send User Data”Enzyme-linked membrane receptors that normally transfer

signals across the cell membrane in response to external signals can go wrong in cancer cells by a variety of ways. Give

any one way in which such receptors can be messed up in cancer cells.

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Receptor Tyrosine Kinase Activation(Enzyme-linked Receptor Activation)

Figure 15-28, Essential Cell Biology, p. 505, Alberts et. al

EnzymeReceptor

Activation of RAS Protein by Activation of Receptor Enzyme Activity; SRC Adapter Protein Functions

Figure 15-29, Essential Cell Biology, p. 506, Alberts et al.

RASnSRC

Ras Signal Sum

RAS Movie on Weinberg CD

Please send in your name under “Send User Data”Ras-protein as a “molecular switch” that is turned on when it binds a small energy-rich molecule. The bound small molecule

that activates Ras-protein is __________________ (give the symbol for the bound molecule).

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G-Protein Activation

G-Protein Activation& DissociationFig 15-15Essential Cell Biologyp. 494Alberts et. al.

GProtAct

Signal Transduction Fig 5-3

GAP = GTPase Activating ProteinMAPK = Mitogen-activated Protein KinasePKA = Protein Kinase A

Transduce

Signal Transduction: Figure 5-3McKinnell, p. 141

Nuclear SignalingG-Protein to NucleusSignal TrnasmissionFig. 15-22 EssentialCell Biology, p. 500

GProt2Nucleus

Normal Cellular Functions for c-Onc-Gene Products (Part 3)(editted from Table 7-3, pp 288-9, Ruddon, 3rd Ed.)

Nuclear Transcription Factors• myc DNA-binding Protein viral transduction• L-myc DNA-bindng Protein? Gene

Amplification• jun DNA-binding Protein viral transduction• fos Transcription Factor with c-jun viral transduction• erbA Thyroxine hormone receptor viral transduction• ets DNA-binding Protein viral transduction• myb DNA-binding Protein viral transduction• lyl-1 DNA-binding Protein Chromosome

translocation

cOncDo3

Prognostic

Normal Cellular Functions for c-Onc-Gene Products (Part 1)(editted from Table 7-3, pp 288-9, Ruddon, 3rd Ed.)

Growth Factors• sis Platelet-derived GF viral transduction• int-2 Fibroblast GF-related viral insertion• int-1 Growth factor? viral insertion

Growth Factor Receptor, Tyrosine Kinase Activity• erbB Epidermal GF receptor (truncated) viral transduction• fms Colony-stimulating GF receptor (mutated) viral transduction• trk Nerve GF receptor? (truncated) DNA transfection• neu Receptor-like (unknown ligand) DNA transfaction• kit Stem-cell GF receptor (truncated) viral transduction

Non-receptor, Cytoplasmic Tyrosine-Kinase Activity• src Membrane-associated viral transduction• fps/fes viral transduction• yes Membrane-associated viral transduction• abl/bcr-abl viral transduction• fgr Membrane-associated homology to src

cOncDo1

G-Protein Inactivation

G-ProteinInactivationFig. 15-16Essential CellBiology,p. 495Alberts et. al.

GProtInactive