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Chapter 5/6: GF,Receptors and Cancer/ Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer Copyright © Garland Science 2007 Cell Signals and Control of Cell Behavior Figure 5.1 The Biology of Cancer (© Garland Science 2007) Ras-Map Kinase Pathway From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Tyrosine Kinase Behavior From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Jak-STAT Signaling Pathway From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Regulation Ras Activity From L. J. Kleinsmith, Principles of Cancer Biology. Copyright (c) 2006 Pearson Benjamin Cummings. Intracellular Protien Kinases • Ras triggers a series of intracellular phosphorylation reaction. • Serine/threonine kinases – BRAF and human melanoma • Intracellular Non-receptor tyrosine kinase – Src kinase – Jak kinase – Abl kinase Other Oncogenes • Transcription Factors – Myc – Fos – erb • Genes involved in driving cell proliferation – Cyclin dependent kinases – Cyclins • Genes involved in inhibiting cell death – BCL-2 Cell to Cell Communication Figure 5.2 The Biology of Cancer (© Garland Science 2007) Src: Protein Tryosine Kinase Figure 5.5a The Biology of Cancer (© Garland Science 2007) Actions of Protein Kinases Figure 5.7a The Biology of Cancer (© Garland Science 2007) EGF Receptor is a Tyrosine Kinase Figure 5.9a The Biology of Cancer (© Garland Science 2007) EGF Receptor and v-ErbB Figure 5.11 The Biology of Cancer (© Garland Science 2007) Deregulation of EGF Receptor Figure 5.12a The Biology of Cancer (© Garland Science 2007) GFs/Receptors and Cancer Table 5.2 The Biology of Cancer (© Garland Science 2007) Receptor Activation Figure 5.15 The Biology of Cancer (© Garland Science 2007) Non-Receptor Tyrosine Kinase Activation Figure 5.20 The Biology of Cancer (© Garland Science 2007) Ras Transformation and GF Signaling Figure 5.32a The Biology of Cancer (© Garland Science 2007) Cytoplasmic Signaling Cascade Signaling Begins at the Cell Surface De novo Synthesis Unnecessary for Immediate Early Gene Expression Signaling Begins at the Cell Surface Serum Induced Changes in Cell Shape Src Protein Domain Structure Structure and Function of SH2 Domains Interaction of Phosphorylated Receptors and Signal Transducers Protein Binding Domains Formation of Multiprotein Complexes SH3 Domains and Ras Activation Kinase Cascades Mediated by Ras Ras Effector Loops Ras Activation of PI3K Activation of PI3K by Ras Docking of PH Domains to PIP3 PI3K/AKT Pathway and Cell Proliferation/Survival Alterations in PI3K Pathway in Human Tumors Other Pathways Involved in Cell Proliferation • • • • • • • Jak-STAT Pathway Integrin Signaling Pathways Wnt-b-Catenin Pathway G-coupled Protein Receptors NfkB Pathway Notch Pathway TGF-B Pathway Jak-STAT Pathway G-Coupled Protein Receptors G-coupled proteins and Cancer Cell Signaling Impacts a Variety of Cellular Processes