Whither goest the RGS proteins?

Studies of the desensitization of G protein-coupled signal transduction hav e led to the discovery of a family of guanosine triphosphatase-activating p roteins (GAPs) for heterotrimeric G protein alpha subunits - the "regulator of G protein signaling" or RGS proteins. In considering both documented an d potential functions of several RGS protein family members with demonstrab le multidomain compositions (p115RhoGEF, PDZRhoGEF, Axin, Axil/Conductin, D -AKAP2, the G protein-coupled receptor kinases [GRKs], the DEP/GGL/RGS subf amily [RGS6, RGS7, RGS9, RGS11], and RGS12), this review explores the shift in our appreciation of the RGS proteins from unidimensional desensitizing agents to multifocal signal transduction regulators.