GTPase-activating proteins for heterotrimeric G proteins: Regulators of G Protein Signaling (RGS) and RGS-like proteins

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858 Scopus citations

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 languageEnglish (US)
Pages (from-to)795-827
Number of pages33
JournalAnnual review of biochemistry
Volume69
DOIs
StatePublished - Nov 2 2000

Keywords

  • GAP
  • GTP-binding protein
  • Scaffold
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry

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