Role of βγ Subunits of G Proteins in Targeting the β-Adrenergic Receptor Kinase to Membrane-Bound Receptors

TLDR

The addition of G protein βγ subunits markedly increases the agonist‑dependent phosphorylation of β₂‑adrenergic receptors and rhodopsin by β‑adrenergic receptor kinase (βARK). Direct activation of βARK cannot explain this effect; instead, βγ subunits bind the COOH‑terminal region of βARK, forming a complex that localizes the kinase to the membrane through the receptor, preferentially with specific βγ complexes, thereby tightly coupling receptor activation to βARK‑mediated desensitization.

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.