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signalling (1).ppt12345777788888885555554
- 1. Topic 14-1 1 14 Cell Signaling
- 2. Topic 14-1 2 Focus on higher order vertebrates Multiple levels of cell signaling Endocrine Cells producing signaling factors are physically separated Messenger molecules are secreted Carried in blood or extra-cellular fluid Target Cells Membrane receptors Intracellular actions via signal cascade Cytoplasmic receptors Usually a specific transport system to move signal molecule- receptor complex to nucleus โ response element Cell Signaling
- 3. Topic 14-1 3 Multiple levels of cell signaling Paracrine Features most similar to endocrine signaling Major difference Target cell found in the same tissue Messenger molecules carried across extra-cellular matrix or through extra-cellular fluid Many growth factors are associated with the matrix Autocrine Cellular self-signaling Cell Signaling
- 4. Topic 14-1 4 Multiple levels of cell signaling Cell Signaling
- 5. Topic 14-1 5 Multiple levels of cell signaling Adhesion Cell to cell interaction Cells identify cell-types nearby Cell to extra-cellular matrix interaction Cells identify their physical environment Cell Signaling
- 6. Topic 14-1 6 Forms of signaling molecules Gasses NO CO Steroid Hormones Testosterone Estradiol Progesterone Glucocorticoids Cortisol Mineralocorticoids Aldosterone Cell Signaling
- 7. Topic 14-1 7 Forms of signaling molecules Neurotransmitters Cell Signaling
- 8. Topic 14-1 8 Forms of signaling molecules Peptide Hormones and Growth Factors Cell Signaling
- 9. Topic 14-1 9 Forms of receptors Steroid receptors Present in the cytoplasm or localized in the nucleus Recall Glucocorticoid receptor โ interaction with the GRE Cell Signaling
- 10. Topic 14-1 10 Forms of receptor G protein-coupled receptors Seven transmembrane helix family Progesterone R b-adrenoceptors Cell Signaling
- 11. Topic 14-1 11 Cell Signaling The b2 adrenoceptor - S- S- Extracellular domain Intracellular domain Transmembrane domain
- 12. Topic 14-1 12 Forms of receptors Tyrosine Kinase Receptors Not only a receptor Also an enzyme Tyrosine kinase Examples Insulin R IGF Type 1 R EGF Cell Signaling
- 13. Topic 14-1 13 Forms of receptors Cytokine superfamily receptors No catalytic domain Interact with nonreceptor protein- tyrosine kinases Src family JAK family Cell Signaling
- 14. Topic 14-1 14 Bla nk The Insulin Receptor Cascades IR is a receptor tyrosine kinase A family of receptors involved in cell growth and differentiation Tetramer Two a and two b subunits Cell Signaling
- 15. Topic 14-1 15 Bla nk The Insulin Receptor Cascades Absence of insulin โ tyrosine kinanse is inactive Binding causes a conformational change Activated tyrosine kinase transfers phosphate groups to: Specific tyrosines of alternate subunit autophosphorylation A soluble protein substrate (family) โ insulin receptor substrates (IRSs) Cell Signaling
- 16. Topic 14-1 16 The Insulin Receptor Cascades Insulin receptor substrates (IRSs) Phosphorylated IRS โ a single function โ to activate downstream messengers Like several other signaling proteins contains an SH2 domain SH2 domains have high affinity for phosphorylated tyrosines Possession of these SH2 modules allows proteins in a signal cascade to be strung together Different cells contain different protein messengers with SH2 domains Insulin signaling varies in effect depending on cell type Cell Signaling
- 17. Topic 14-1 17 The Insulin Receptor Cascades Insulin receptor substrates (IRSs) Insulin may signal along several independent pathways One of these is phosphatidylinositol-3-hydroxy kinase (PI3K) Cell Signaling
- 18. Topic 14-1 18 Blan k Cell Signaling The Insulin Receptor Cascades Phosphatidylinositol-3-hydroxy kinase (PI3K) Catalyses phosphate addition to the 3โ position on the sugar ring of phosphatidyl inositol Products: PI 3,4-biphosphate (PIP2) PI 3,4,5-triphosphate (PIP3) Remain in the cytosolic leaflet of lipid bilayer Membrane-bound lipid messengers Diverse functions in many cell types Activation of protein kinase B via its PH domain
- 19. Topic 14-1 19 Cell Signaling The Insulin Receptor Cascades Phosphatidylinositol-3- hydroxy kinase (PI3K)
- 20. Topic 14-1 20 Cell Signaling The Insulin Receptor Cascades Protein kinase B PIP2 recruits PKB to plasma membrane Binding โ conformational change Transfer of glucose transporters to the plasma membrane Increased protein synthesis Glycogen synthase Glucose to glycogen
- 21. Topic 14-1 21 The Insulin Receptor Cascades Insulin receptor substrates (IRSs) Insulin may signal along several independent pathways Another IRS pathway: Ras โ cell growth and proliferation Cell Signaling
- 22. Topic 14-1 22 The Insulin Receptor Cascades Ras ras gene - originally discovered as a viral oncogene Also part of the normal genome Many tumor cells contain a mutant ras Protein product Ras Small G-protein At inner surface of plasma membrane Lipid group embedded in inner leaflet Cell Signaling