Biology of Cancer - Dr. Jennifer Staiger

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Transcript 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 – MDM-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 PIP 3

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