GAIP and RGS4 Are GTPase-activating Proteins for the Gi Subfamily of G Protein Alpha Subunits

Cell. 1996 Aug 9;86(3):445-52. doi: 10.1016/s0092-8674(00)80117-8.

Abstract

A novel class of regulators of G protein signaling (RGS) proteins has been identified recently. Genetic evidence suggests that RGS proteins inhibit G protein-mediated signaling at the level of the receptor-G protein interaction or the G protein alpha subunit itself. We have found that two RGS family members, GAIP and RGS4, are GTPase-activating proteins (GAPs), accelerating the rate of GTP hydrolysis by Gi alpha 1 at least 40-fold. All Gi subfamily members assayed were substrates for these GAPs; Gs alpha was not. RGS4 activates the GTPase activity of certain Gi alpha 1 mutants (e.g., R178C), but not others (e.g., Q204L). The GAP activity of RGS proteins is consistent with their proposed role as negative regulators of G protein-mediated signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • DNA, Complementary / analysis
  • Escherichia coli
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • GTPase-Activating Proteins
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Humans
  • Hydrolysis
  • Magnesium / pharmacology
  • Molecular Sequence Data
  • Mutation
  • Phosphoproteins / metabolism*
  • Polymerase Chain Reaction
  • Proteins / metabolism*
  • RGS Proteins*
  • Temperature

Substances

  • DNA, Complementary
  • GTPase-Activating Proteins
  • Phosphoproteins
  • Proteins
  • RGS Proteins
  • regulator of G-protein signalling 19
  • Guanosine Diphosphate
  • RGS4 protein
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • Magnesium