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CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer

CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer. Signaling cascades. A signaling pathway reaches from the cell surface into the nucleus. Expression of immediate early genes. cycloheximide. Immediate vs. delayed early genes.

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CHAPTER 6 Cytoplasmic Signaling Circuitry Programs Many of the Traits of Cancer

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  1. 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

  10. Structure and function of Src

  11. 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

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

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

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

  15. Biochemistry of lipid bilayers

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

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

  18. Docking of PH domains to PIP3

  19. AKT/PKB and the control of cell growth

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

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

  22. Constitutive activation of STAT3

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

  24. Anoikis and morphogenesis

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

  26. Regulation of b-catenin signaling

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

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

  29. Deregulation of dual-address pathways in human cancers

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

  31. Two-dimensional signaling maps

  32. Raseffector pathways

  33. Frequencies of oncogene activation in various human tumors

  34. Structure of a signaling pathway

  35. 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?

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