Abstract
Recent progress on the activation of G protein-coupled receptor kinases is reviewed. β-Adrenergic receptor kinase (βARK) is activated by G protein βγ-subunits, which interact with the carboxyl terminal portion of βARK. Muscarinic receptor m2-subtypes are phosphorylated by βARK1 in the central part of the third intracellular loop (I3). Phosphorylation of I3-GST fusion protein by βARK1 is synergistically stimulated by the βγ-subunits and mastoparan or a peptide corresponding to portions adjacent to the transmembrane segments of m2-receptors or by βγ-subunits and the agonist-bound I3-deleted m2 variant. These results indicate that agonist-bound receptors serve as both substrates and activators of βARK.
