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Intracellular Communication: Different Receptors Types

Intracellular Communication: Different Receptors Types. G Protein Coupled Receptors (GPCR). A G-Protein-Coupled Receptor Or G Protein-linked Receptor 7 transmembrane domains. The disassembly of G-Protein upon stimulation

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Intracellular Communication: Different Receptors Types

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  1. Intracellular Communication: Different Receptors Types

  2. G Protein Coupled Receptors (GPCR)

  3. A G-Protein-Coupled Receptor Or G Protein-linked Receptor 7 transmembrane domains

  4. The disassembly of G-Protein upon stimulation Spontaneous deactivation is very fast, in minutes. However, with the help of RGS (regulator of G protein signaling, a GAP for a unit), signals can be shut off even faster

  5. The Activation cycle of G-Protein

  6. GPCR Signaling: cAMP

  7. The visualization of cAMP in nerve cells GPCR->Gs->adenylyl cyclase->cAMP Gi

  8. cAMP cycle: GPCR->Gs->adenylyl cyclase->cAMP Cyclic AMP phosphodiesterase breaks down cAMP to 5’-AMP

  9. The function of cAMP Targeting PKA (cyclic-AMP-dependent protein kinase A)

  10. The Whole Signaling Network related to cAMP

  11. Terminology: CRE(cyclic AMP response element); CREB: CRE binding protein; CBP: CREB binding protein

  12. GPCR Signaling: Calcium

  13. Three Types of Inositol phospholipids PI, PI(4)P, PI(4,5)P2

  14. Phospholipase C-b (PLC-b) Produces DAG (diacylglycerol) and IP3 (inositol 1,4,5-trisphosphate (IP3)) Gq->PLC-b

  15. Gq signaling pathways and Calcium

  16. Fertilization of an egg by a sperm triggering an increase in cytosolic Calcium • 3 major types of calcium channels: • Voltage dependent Ca channels on plasma membrane • IP3-gated Ca release channels on ER membrane • Ryanodine receptor on ER membrane

  17. Calcium uptake and deprivation • Na/Ca exchanger on plasma membrane, 2. Ca pump on ER membrane, 3. Ca binding molecules, 4. Ca pump on Mitochondia

  18. Calcium Frequency encoding signaling strength Local Ca blips, sparks, puffs, reflecting local opening of individual channels in ER, strong local signal induces global activity, the elevated Calcium trigger calcium deprivation system

  19. Targeting molecules for Calcium Calcium binding protein Calmodulin

  20. Ca2+/calmodulin dependent protein kinase (CaM-kinase) Memory function: 1. calmodulin dissociate after 10 sec of low calcium level; 2. remain active after calmodulin dissociation

  21. Ca2+/calmodulin dependent protein kinase (CaM-kinase) Frequency decoder of Calcium oscillation High frequence, CaM-kinase does not return to basal level before the second wave of activation starts

  22. Desensitization of GPCR 1. Inhibitory structural alteration of receptor; 2. receptor internalization; 3. receptor degration GRK (G protein-linked receptor kinase) Arrestin takes to clathrin-coated pits and degradation

  23. GPCR Signaling Summary • 1. G-protein types • 2. cAMP and Calcium signaling pathways • 3. desensitization

  24. Enzyme-Linked Cell Surface Receptors • *Receptor Tyrosine Kinase • *Tyrosine kinase associated receptors • *Receptor-like tyrosine phosphatase • *Receptor serine/threonine kinase • Receptor guanylyl cyclase • Histidine like associated receptor

  25. Receptor Tyrosine Kinases (RTKs)

  26. Seven subfamilies of receptor tyrosine kinases

  27. Three ways in which signaling proteins can cross-link receptor chains 1. dimer, 2. monomer but brought together by proteoglycan, 3. cluster on membrane

  28. The importance of receptor oligomerization

  29. The docking of signaling molecules at RTK

  30. The binding of SH2-containing intracellular signaling proteins to an activated PDGF receptor

  31. The structural view of SH2 domain

  32. RTK Signaling: Ras Pathway

  33. The regulation of Ras activity, a famous downstream molecule of RTK responsible for cancer development

  34. The activation of Ras by RTK signaling

  35. The MAP-kinase regulated by Ras

  36. RTK Signaling: PI3K Pathway

  37. The inositol phospholipids generated by PI3K

  38. The recruitment of signaling molecules with PH domains to the plasma membrane during B cell activation One PI3K pathway PH domain: pleckstrin homology domain

  39. Another PI3K pathway to regulate cell survival

  40. Another PI3K pathway to regulate cell migration PI3K->PIP3->GEF->Rac->Wave->Arp2/3->Actin polymerization

  41. Intracellular Signaling Pathways activated by RTKs and GPCRs

  42. Tyrosine kinase associated receptors • Integrins: cell-extracellular matrix adhesion • Binding to Src and FAK

  43. Receptorlike tyrosine phosphatases • Intracellular protein and receptor

  44. Receptor Serine/threonine kinase • Transforming growth factor (TGF-b) and Smad signaling pathway

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