The beta-adrenergic receptor kinase interacts with the amino terminus of the G protein beta subunit.

Desensitization of G protein-coupled receptors involves phosphorylation of the receptors by G protein-coupled receptor kinases, such as the beta-adrenergic receptor kinase (beta ARK). beta ARK activity depends upon its translocation from the cytoplasm to the membrane. The beta gamma subunits of G proteins bind to beta ARK and recruit the kinase to the membrane. The G beta gamma binding domain is localized to a carboxyl terminal region of beta ARK but the beta ARK binding domain of G beta gamma is not known. We used the yeast two-hybrid assay to characterize the interaction between G beta and beta ARK. We demonstrate an interaction between the carboxyl terminus of beta ARK and G beta 2. The strength of this interaction is increased when the VP16 transactivation domain is placed on the carboxyl end of G beta 2, indicating that an accessible G beta 2 amino terminus is important for its interaction with beta ARK. In addition, we show that amino acids 1 to 145 of G beta 2 are sufficient for beta ARK binding.