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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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A G-Protein-Coupled Receptor

Or G Protein-linked Receptor

7 transmembrane domains


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


The visualization of cAMP in nerve cells

GPCR->Gs->adenylyl cyclase->cAMP



cAMP cycle: GPCR->Gs->adenylyl cyclase->cAMP

Cyclic AMP phosphodiesterase breaks down cAMP to 5’-AMP


The function of cAMP

Targeting PKA (cyclic-AMP-dependent protein kinase A)


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


Phospholipase C-b

(PLC-b) Produces DAG (diacylglycerol) and IP3 (inositol 1,4,5-trisphosphate (IP3))



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

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

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


Targeting molecules for Calcium

Calcium binding protein Calmodulin


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


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


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


GPCR Signaling Summary

  • 1. G-protein types
  • 2. cAMP and Calcium signaling pathways
  • 3. desensitization

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

Three ways in which signaling proteins can cross-link receptor chains

1. dimer, 2. monomer but brought together by proteoglycan, 3. cluster on membrane


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


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


The recruitment of signaling molecules with PH domains to the plasma membrane during B cell activation

One PI3K pathway

PH domain: pleckstrin homology domain


Another PI3K pathway to regulate cell migration

PI3K->PIP3->GEF->Rac->Wave->Arp2/3->Actin polymerization


Tyrosine kinase associated receptors

  • Integrins: cell-extracellular matrix adhesion
  • Binding to Src and FAK

Receptorlike tyrosine phosphatases

  • Intracellular protein and receptor

Receptor Serine/threonine kinase

  • Transforming growth factor (TGF-b) and Smad signaling pathway

Enzyme-linked Receptor Signaling Summary

  • 1. receptor types
  • 2. RTK and its signaling: Ras and PI3K
  • 3. Tyrosine kinase associated receptors and Receptor-like tyrosine phosphatase
  • 4. Receptor serine/threonine kinase, TGF-b and Smad