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

Desensitization of G protein-coupled receptors involves phosphorylation of the receptors by G protein-coupled receptor kinases, such as the β-adrenergic receptor kinase (βARK). βARK activity depends upon its translocation from the cytoplasm to the membrane. The βγ subunits of G proteins bind to βARK and recruit the kinase to the membrane. The Gβγ binding domain is localized to a carboxyl terminal region of βARK but the βARK binding domain of Gβγ is not known. We used the yeast two-hybrid assay to characterize the interaction between Gβ and βARK. We demonstrate an interaction between the carboxyl terminus of βARK and Gβ₂. The strength of this interaction is increased when the VP16 transactivation domain is placed on the carboxyl end of Gβ₂, indicating that an accessible Gβ₂ amino terminus is important for its interaction with βARK. In addition, we show that amino acids 1 to 145 of Gβ₂ are sufficient for βARK binding.