Download Biology of Cancer - Dr. Jennifer Staiger

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
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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