Abstract

The rate and extent of the agonist-dependent phosphorylation of β 2 -adrenergic receptors and rhodopsin by β-adrenergic receptor kinase (βARK) are markedly enhanced on addition of G protein βγ subunits. With a model peptide substrate it was demonstrated that direct activation of the kinase could not account for this effect. G protein βγ subunits were shown to interact directly with the COOH-terminal region of βARK, and formation of this βARK-βγ complex resulted in receptor-facilitated membrane localization of the enzyme. The βγ subunits of transducin were less effective at both enhancing the rate of receptor phosphorylation and binding to the COOH-terminus of βARK, suggesting that the enzyme preferentially binds specific βγ complexes. The βγ-mediated membrane localization of βARK serves to intimately link receptor activation to βARK-mediated desensitization.