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Outline of Signal Transduction section: Lecture 1- Introduction and Growth Factor Receptors

Outline of Signal Transduction section: Lecture 1- Introduction and Growth Factor Receptors Lecture 2- Signaling through G protein-coupled Receptors Lecture 3- Effectors of RTKs and GPCR signaling Lecture 4- Signals to the nucleus: growth, differentiation and death. IBS 501

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Outline of Signal Transduction section: Lecture 1- Introduction and Growth Factor Receptors

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  1. Outline of Signal Transduction section: Lecture 1- Introduction and Growth Factor Receptors Lecture 2- Signaling through G protein-coupled Receptors Lecture 3- Effectors of RTKs and GPCR signaling Lecture 4- Signals to the nucleus: growth, differentiation and death

  2. IBS 501 Introduction to Cell Biology Lecture 1 Introduction and Growth Factor Receptors Instructor: Karl Saxe Readings: Lodish et al., pages 848-862; 871-878; Alberts et al., pages 481-493; 504-509.

  3. Cell-to-cell communication by extracellular signaling usually involves six steps • (1) synthesis of the signaling molecule by the signaling cell • (2) release of the signaling molecule by the signaling cell • (3) transport of the signal to the target cell • (4) detection of the signal by a specific receptor protein • (5) a change in cellular metabolism, function, or development triggered by the receptor-signal complex • (6) removal of the signal, which usually terminates the cellular response

  4. Signaling molecules operate over various distances in animals Receptor proteins exhibit ligand-binding and effector specificity

  5. Hormones can be classed based on their solubility and receptor location

  6. Cell-surface receptors belong to four major classes

  7. Cell-surface receptors belong to four major classes

  8. Receptor tyrosine kinases and Ras • Receptor tyrosine kinases recognize soluble or membrane bound peptide/protein hormones that act as growth factors • Binding of the ligand stimulates the receptor’s tyrosine kinase activity, which subsequently stimulates a signal-transduction cascade leading to changes in cell physiology and/or patterns of gene expression • RTK pathways are involved in regulation of cell proliferation and differentiation, promotion of cell survival, and modulation of cellular metabolism • RTKs transmit a hormone signal to Ras, a GTPase switch protein that passes on the signal on to downstream components

  9. Families of Growth Factor Receptors

  10. Ligand binding leads to autophosphorylation of RTKs

  11. Conserved proteins function in signal transduction: adapter proteins

  12. Partners for PDGF-R

  13. Conserved proteins function in signal transduction: GTPase switch proteins

  14. Ras cycles between active and inactive forms

  15. ras-GTP-Mg++ ras-GDP-Mg++

  16. An adapter protein and GEF link most activated RTKs to Ras

  17. Partners for PDGF-R

  18. Signaling modules

  19. Activation of PDGF-R

  20. Other conserved proteins function in signal transduction: protein kinases and phosphatases

  21. Common signaling pathways are initiated by different receptors in a class

  22. Signals that induce EGFR transactivation

  23. Mechanisms of EGFR transactivation

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