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.