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 Galpha and the Gbetagamma 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 PI3Kgamma by Gbetagamma 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 PLCbeta to mediate activation of PKC and CaMKII, which can have either stimulatory or inhibitory consequences for the downstream MAPK pathway
