RGS4 and GAIP are GTPase-activating proteins for Gq alpha and block activation of phospholipase C beta by gamma-thio-GTP-Gq alpha.
RGS proteins constitute a newly appreciated and large group of negative regulators of G protein signaling. Four members of the RGS family act as GTPase-activating proteins (GAPs) with apparent specificity for members of the Gi alpha subfamily of G protein subunits. We demonstrate here that two RGS proteins, RGS4 and GAIP, also act as GAPs for Gq alpha, the G alpha protein responsible for activation of phospholipase C beta. Furthermore, these RGS proteins block activation of phospholipase C beta by guanosine 5'-(3-O-thio) triphosphate-Gq alpha. GAP activity does not explain this effect, which apparently results from occlusion of the binding site on G alpha for effector. Inhibitory effects of RGS proteins on G protein-mediated signaling pathways can be demonstrated by simple mixture of RGS4 or GAIP with plasma membranes.
Hepler
J R
JR
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235-9041, USA.
Berman
D M
DM
Gilman
A G
AG
Kozasa
T
T
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology*; D020690:GTPase-Activating Proteins; D006160:Guanosine Triphosphate / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D054799:Phospholipase C beta; D010750:Phosphoproteins / Q000502:physiology*; D011506:Proteins / Q000502:physiology*; D020710:RGS Proteins; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*
D020690:GTPase-Activating Proteins; D007527:Isoenzymes; D010750:Phosphoproteins; D011506:Proteins; D020710:RGS Proteins; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; C097187:regulator of G-protein signalling 19; C098799:RGS4 protein; D006160:Guanosine Triphosphate; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases