RGS4 and GAIP are GTPase-activating proteins for G(q alpha) and block activation of phospholipase C beta by gamma-thio-GTP-G(q alpha)

RGS proteins constitute a newly appreciated and large group of negative regulators of G protein signaling. Pour members of the RGS family act as GTPase-activating proteins (GAPs) with apparent specificity for members of the G(i alpha) subfamily of G protein subunits. We demonstrate here that two RGS proteins, RGS4 and GAIP, also act as GAPs for G(q 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-G(q 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.