GTPase-activating proteins for heterotrimeric G proteins: Regulators of G protein signaling (RGS) and RGS-like proteins

GTPase-activating proteins (GAPs) regulate heterotrimeric G proteins by increasing the rates at which their cr subunits hydrolyze bound GTP and thus return to the inactive state. G protein GAPs act allosterically on Ga: subunits, in contrast to GAPs for the Ras-like monomeric GTP-binding proteins. Although they do not contribute directly to the chemistry of GTP hydrolysis, G protein GAPs can accelerate hydrolysis >2000-fold, G protein GAPs include both effector proteins (phospholipase C-beta, p115RhoGEF) and a growing family of regulators of G protein signaling (RGS proteins) that are found throughout the animal and fungal kingdoms. GAP activity can sharpen the termination of a signal upon removal of stimulus, attenuate a signal either as a feedback inhibitor or in response to a second input, promote regulatory association of other proteins, or redirect signaling within a G protein signaling network. GAPs are regulated by various controls of their cellular concentrations, by complex interactions with G beta gamma or with G gamma 5 through an endogenous G gamma-like domain, and by interaction with multiple other proteins.