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