RGS4 and GAIP are GTPase-activating proteins for G(qα) and block activation of phospholipase Cβ by γ-thio-GTP-G(qα)

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 G(iα) subfamily of G protein subunits. We demonstrate here that two RGS proteins, RGS4 and GAIP, also act as GAPs for G(qα), the G(α) protein responsible for activation of phospholipase Cβ. Furthermore, these RGS proteins block activation of phospholipase Cβ by guanosine 5′-(3-O-thio)triphosphate-G(qα). GAP activity does not explain this effect, which apparently results from occlusion of the binding site on G(α) 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.