ACTIVATION BY G-PROTEIN BETA-GAMMA-SUBUNITS OF BETA-ADRENERGIC AND MUSCARINIC RECEPTOR KINASE

We have shown previously that GTP-binding regulatory protein (G protein) betagamma subunits stimulate the agonist- or light-dependent phosphorylation of muscarinic acetylcholine receptors (mAChRs) and rhodopsin by a protein kinase partially purified from porcine brain (mAChR kinase) but not the phosphorylation of rhodopsin by rhodopsin kinase (Haga, K., and Haga, T. (1992) J. Biol. Chem. 267, 2222-2227). We report here that the mAChR kinase phosphorylates beta-adrenergic receptors (beta-ARs) purified from bovine lung in an agonist-dependent manner, and the phosphorylation is also stimulated by G protein betagamma subunits. We also report that recombinant beta-adrenergic receptor kinase 1 (beta-ARK1) expressed in COS-7 cells phosphorylates mAChRs (human m2 subtype) and rhodopsin in an agonist- or light-dependent manner, respectively, and that this phosphorylation is stimulated by G protein betagamma subunits. By contrast, the betagamma subunits do not stimulate the phosphorylation of mAChRs or rhodopsin by a beta-ARK1 mutant lacking a part of the carboxyl-terminal region which is present in beta-ARKs but not in rhodopsin kinase. These results indicate that the beta-ARK1 is the same as or very similar to the mAChR kinase but is distinguished from the rhodopsin kinase with respect to activation by the betagamma subunits and that the extra carboxyl-terminal sequence in beta-ARKs is required for the stimulation by the betagamma subunits.