Abstract
GTPase-activating proteins (GAPs) regulate heterotrimeric G proteins by increasing the rates at which their α subunits hydrolyze bound GTP and thus return to the inactive state. G protein GAPs act allosterically on Gα 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-β, 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 Gβγ or with Gβ5 through an endogenous Gγ-like domain, and by interaction with multiple other proteins.
Original language | English (US) |
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Pages (from-to) | 795-827 |
Number of pages | 33 |
Journal | Annual review of biochemistry |
Volume | 69 |
DOIs | |
State | Published - 2000 |
Keywords
- GAP
- GTP-binding protein
- Scaffold
- Signal transduction
ASJC Scopus subject areas
- Biochemistry