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LIFE 210 (38)

GPCR, cAMP, PKA, calmodulin, CAM-kinase

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Colorado State University
Life Science
LIFE 210
Paul Laybourn

31 October A G-protein coupled receptor (GPCR) is a 7 pass transmembrane protein They use G proteins to relay signals into the cell interior GPCR pathways are targets of half of all known drugs Trimeric (α, β, γ) Inactive when the α subunit has GDP bound α and γ attached by lipids GPCR activation induces the α subunit to release GDP to bind GTP An active GPCR catalyzes the activation of many molecules of G protein Active G protein regulates enzymes or ion channels in the plasma membrane (conformational change) Some G proteins regulate production of cyclic-AMP Synthesized by adenylyl cyclase and degraded by a phosphodiesterase Extracellular signals can increase cAMP 20x in a few seconds Different cell types respond differently to increases in cAMP One cell type often responds in the same way, regardless of the extracellular signal that causes it. This is because the receptors are different; they bind the same signal, but relay the message differently. Cyclic AMP-dependent protein kinase (PKA) mediates most of the effects of cyclic AMP It phosphorylates different target proteins according to the cell type; this produces different effects Some responses mediated by cyclic-AMP depend on gene transcription and take hours A short cyclic AMP signal can be transformed into a long-term change in the cell. Ex learning and memory, hormone production REB binds to the cyclic AMP site on a gene once activated Some G proteins regulate the plasma membrane-bound enzyme phospholipase C-β It secretes IP (3oluble) and diacylglyercol (remains in the plasma membrane) Ca release from ER and activation of PKC at the plasma membrane 2+ Inositol 1, 4, 5 (IP3) release
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