G-protein coupled receptors (GPCRs) are activated by a wide variety of external stimuli. Upon receptor activation the G protein exchanges GDP for GTP, causing the dissociation of the GTP-bound Ga and the Gbg subunits, triggering diverse signaling cascades. Receptors coupled to different heterotrimeric G protein subtypes can utilize different scaffolds to activate the small G protein/MAPK cascade, employing at least three different classes of tyrosine kinases. Src family kinases are recruited following activation of PI(3)Kg by Gbg subunits. They are also recruited by receptor internalization, cross-activation of receptor tyrosine kinases, or by signaling through an integrin scaffold involving Pyk2 and/or FAK. GPCRs can also employ PLCb to mediate activation of PKC and CaM-KII, which can have either stimulatory or inhibitory consequences for the downstream MAPK pathwayref1, ref2, ref3, ref4.
Copyright © 2001-2014 Daniele Focosi.
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