Phosducin is a protein kinase A-regulated G-protein regulator

SIGNAL transduction by G-protein-coupled receptors is regulated by various mechanisms acting at the receptor level; those studied most thoroughly are from the β-adrenergic receptor/G s /adenylyl cyclase system 1–3 . We report here a regulatory mechanism occurring at the level of the G proteins themselves. A protein with M r 33,000 that inhibits G s -GTPase activity was purified from bovine brain. This protein is very similar or identical to phosducin, a protein previously thought to be specific for retina and pineal gland 4–8 . Recombinant phosducin inhibited the GTPase activity of several G proteins, and also inhibited G s -mediated adenylyl cyclase activation. Blockade of its inhibitory effects by protein kinase A suggests that phosducin may be part of a complex regulatory network controlling G-protein-mediated signalling.