CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer
-
Upload
emma-levine -
Category
Documents
-
view
30 -
download
0
description
Transcript of CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer
![Page 1: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/1.jpg)
CHAPTER 6
Cytoplasmic Signaling Circuitry
Programs Many of the Traits of Cancer
Signaling cascades
![Page 2: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/2.jpg)
A signaling pathway reaches from the cell surface into the nucleus
Expression of immediate early genes
![Page 3: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/3.jpg)
Immediate vs. delayed early genes
cycloheximide
![Page 4: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/4.jpg)
Serum-induced alterations of cell shape.
![Page 5: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/5.jpg)
The Ras protein stands in the middle of a complex signaling cascade
Structure of the fly eye.
Son of sevenless
![Page 6: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/6.jpg)
Tyrosine phosphorylation controls the location and thereby the actions of many cytoplasmic signaling proteins
Domain structure of the Src protein
![Page 7: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/7.jpg)
Structure and function of SH2 and SH3 domains
![Page 8: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/8.jpg)
Attraction of signal-transducing proteins by phosphorylated receptors
![Page 9: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/9.jpg)
Protein interaction domains as modular units of protein structure
![Page 10: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/10.jpg)
![Page 11: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/11.jpg)
Structure and function of Src
![Page 12: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/12.jpg)
SH2 and SH3 groups explain how growth factor receptors activate Ras and acquire signaling specificity
Intermolecular links forgets by the Grb2 and Shc bridging proteins
![Page 13: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/13.jpg)
Ras-regulated signaling pathways: A cascade of kinases forms one of three important signaling pathways downstream of Ras
The Ras effector loop
![Page 14: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/14.jpg)
The Ras ->Raf ->MAP kinase pathway
![Page 15: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/15.jpg)
Ras-regulated signaling pathways: a second downstream pathway controls inositol lipids and the Akt/PKB kinase
The PI3K kinase pathway
![Page 16: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/16.jpg)
Biochemistry of lipid bilayers
![Page 17: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/17.jpg)
Activation of PI3K by Ras, growth factor receptors and somatic mutation.
![Page 18: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/18.jpg)
Migration of PH-containing proteins to PIP3 in the plasma membrane
![Page 19: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/19.jpg)
Docking of PH domains to PIP3
![Page 20: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/20.jpg)
AKT/PKB and the control of cell growth
![Page 21: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/21.jpg)
![Page 22: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/22.jpg)
![Page 23: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/23.jpg)
Ras-regulated signaling pathways: a third downstream pathway acts through Ral, a distant cousin of Ras
Ral and the control of cytoskeleton
![Page 24: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/24.jpg)
The Jak–STAT pathway allows signals to be transmitted from the plasma membrane directly to the nucleus
![Page 25: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/25.jpg)
Constitutive activation of STAT3
![Page 26: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/26.jpg)
Cell adhesion receptors emit signals that converge with those released by growth factor receptors
Integrin signaling
![Page 27: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/27.jpg)
Anoikis and morphogenesis
![Page 28: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/28.jpg)
Multiple roles of b-catenin
The Wnt– -catenin pathway contributes to cell βproliferation
![Page 29: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/29.jpg)
Regulation of b-catenin signaling
![Page 30: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/30.jpg)
G-protein–coupled receptors can also drive normal and neoplastic proliferation
![Page 31: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/31.jpg)
![Page 32: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/32.jpg)
Four additional “dual-address” signaling pathways contribute in various ways to normal and neoplastic proliferation
![Page 33: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/33.jpg)
Deregulation of dual-address pathways in human cancers
![Page 34: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/34.jpg)
Well-designed signaling circuits require both negative and positive feedback controls
![Page 35: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/35.jpg)
Two-dimensional signaling maps
![Page 36: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/36.jpg)
Ras effector pathways
![Page 37: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/37.jpg)
Frequencies of oncogene activation in various human tumors
![Page 38: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/38.jpg)
Structure of a signaling pathway
![Page 39: CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer](https://reader030.fdocuments.in/reader030/viewer/2022033020/56813552550346895d9cb319/html5/thumbnails/39.jpg)
Homework:
Due on 10/27 (Monday), 6 PM Handwritten only, no electronic version, within 5 A4 pages.
Q:Please describe the Warburg effect of cancer cells. What’s the molecular mechanism and application?