1. Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer
CHAPTER 6
Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer
Signaling cascades

2. A signaling pathway reaches from the cell surface into the nucleus
Expression of immediate early genes

3. cycloheximide
Immediate vs. delayed early genes

4. Serum-induced alterations of cell shape.

5. The Ras protein stands in the middle of a complex signaling cascade
Structure of the fly eye.
Son of sevenless

6. Tyrosine phosphorylation controls the location and thereby the actions of many cytoplasmic signaling proteins
Domain structure of the Src protein

7. Structure and function of SH2 and SH3 domains

8. Attraction of signal-transducing proteins by phosphorylated receptors

9. Protein interaction domains as modular units of protein structure

11. Structure and function of Src

12. 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

13. Ras-regulated signaling pathways: A cascade of kinases forms one of three important signaling pathways downstream of Ras
The Ras effector loop

14. The Ras ->Raf ->MAP kinase pathway

15. Ras-regulated signaling pathways: a second downstream pathway controls inositol lipids and the Akt/PKB kinase
The PI3K kinase pathway

16. Biochemistry of lipid bilayers

17. Activation of PI3K by Ras, growth factor receptors and somatic mutation.

18. Migration of PH-containing proteins to PIP3 in the plasma membrane

19. Docking of PH domains to PIP3

20. AKT/PKB and the control of cell growth

23. Ras-regulated signaling pathways: a third downstream pathway acts through Ral, a distant cousin of Ras
Ral and the control of cytoskeleton

24. The Jak–STAT pathway allows signals to be transmitted from the plasma membrane directly to the nucleus

25. Constitutive activation of STAT3

26. Cell adhesion receptors emit signals that converge with those released by growth factor receptors
Integrin signaling

27. Anoikis and morphogenesis

28. The Wnt–β-catenin pathway contributes to cell proliferation
Multiple roles of b-catenin

29. Regulation of b-catenin signaling

30. G-protein–coupled receptors can also drive normal and neoplastic proliferation

32. Four additional “dual-address” signaling pathways contribute in various ways to normal and neoplastic proliferation

33. Deregulation of dual-address pathways in human cancers

34. Well-designed signaling circuits require both negative and positive feedback controls

35. Two-dimensional signaling maps

36. Ras effector pathways

37. Frequencies of oncogene activation in various human tumors

38. Structure of a signaling pathway

39. 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?