GAIP and RGS4 are GTPase-activating proteins for the Gi subfamily of G protein alpha subunits.
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.
Berman
D M
DM
Department of Pharmacology University of Texas Southwestern Medical Center Dallas 75235, USA.
Wilkie
T M
TM
Gilman
A G
AG
D001483:Base Sequence; D018076:DNA, Complementary / Q000032:analysis; D004926:Escherichia coli; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008274:Magnesium / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000378:metabolism*; D020710:RGS Proteins; D013696:Temperature
D018076:DNA, Complementary; D020690:GTPase-Activating Proteins; D010750:Phosphoproteins; D011506:Proteins; D020710:RGS Proteins; C097187:regulator of G-protein signalling 19; D006153:Guanosine Diphosphate; C098799:RGS4 protein; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D008274:Magnesium