title: Protein kinases that phosphorylate activated G protein-coupled receptors.
abstract: G protein-coupled receptor kinases (GRKs) are a family of serine/threonine protein kinases that specifically recognize agonist-occupied, activated G protein-coupled receptor proteins as substrates. Phosphorylation of an activated receptor by a GRK terminates signaling by that receptor, by initiating the uncoupling of the receptor from heterotrimeric G proteins. Six distinct mammalian GRKs are known, which differ in tissue distribution and in regulatory properties. The intracellular localization of GRKs to membrane-bound receptor substrates is the most important known regulatory feature of these enzymes. Rhodopsin kinase (GRK1) requires a post-translationally added farnesyl isoprenoid to bind to light-activated rhodopsin. The beta-adrenergic receptor kinases (GRK2 and GRK3) associate with heterotrimeric G protein beta gamma-subunits, released upon receptor activation of G proteins, for membrane anchorage. The recently-described GRKs 4, 5, and 6 comprise a distinct subgroup of GRKs. These kinases utilize distinct mechanisms for membrane localization, which are just beginning to be defined. All GRKs appear to play the same general cellular role of desensitizing activated G protein-coupled receptors, but utilize distinctly individual means to the same end.
authors.affiliation: Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Premont
authors.forename: J
authors.initials: J
authors.lastname: Inglese
authors.forename: R J
authors.initials: RJ
authors.lastname: Lefkowitz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D005136:Eye Proteins; D051606:G-Protein-Coupled Receptor Kinase 1; D019204:GTP-Binding Proteins / Q000378:metabolism*; D008322:Mammals; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D005136:Eye Proteins; D011494:Protein Kinases; D020794:Receptor Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D051606:G-Protein-Coupled Receptor Kinase 1; D019204:GTP-Binding Proteins