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

Annu Rev Biochem. 2000:69:795-827. doi: 10.1146/annurev.biochem.69.1.795.


GTPase-activating proteins (GAPs) regulate heterotrimeric G proteins by increasing the rates at which their subunits hydrolyze bound GTP and thus return to the inactive state. G protein GAPs act allosterically on G 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-¿, 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¿ or with G¿5 through an endogenous G-like domain, and by interaction with multiple other proteins.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Conserved Sequence
  • GTPase-Activating Proteins / chemistry*
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism*
  • Heterotrimeric GTP-Binding Proteins / chemistry*
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Humans
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Phylogeny
  • Potassium Channels / metabolism
  • Protein Structure, Tertiary
  • RGS Proteins / chemistry*
  • RGS Proteins / genetics
  • RGS Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Signal Transduction


  • GTPase-Activating Proteins
  • Potassium Channels
  • RGS Proteins
  • Heterotrimeric GTP-Binding Proteins