Regulation of G protein-coupled receptor kinase 2

Abstract

Publisher Summary G protein-coupled receptor kinase 2 (GRK2) was originally termed a “β-adrenergic receptor kinase” (βARK) because it was purified as a kinase of the adrenergic β 2 receptor, and the adrenergic β 2 receptor was the only known substrate of GRK2. GRK2 is now known to phosphorylate different kinds of G protein-coupled receptors (GPCRs), including rhodopsin, muscarinic acetylcholine receptors, and adrenergic β2 receptors when they are stimulated by light absorption or agonist binding. There is no appreciable homology among amino acid sequences around phosphorylation sites in these GPCRs, except that they are flanked by acidic amino acid residues. The substrate specificity of GRK2, however, is strict in a sense that only a few proteins are known to be substrates of GRK2 besides agonist bound GPCRs. One of the reasons why agonist-bound GPCRs are phosphorylated by GRK2 is that GRK2 is activated by agonist-bound receptors. Very recently, tubulin, synuclein, and phosducin have been reported to be phosphorylated by GRK2, but it is not known whether they serve as activators of GRK2 and why they are substrates of GRK2 unless they are activators.