G protein-coupled receptor kinases.
G protein-coupled receptor kinases (GRKs) constitute a family of six mammalian serine/threonine protein kinases that phosphorylate agonist-bound, or activated, G protein-coupled receptors (GPCRs) as their primary substrates. GRK-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signaling, or desensitization. This review focuses on the regulation of GRK activity by a variety of allosteric and other factors: agonist-stimulated GPCRs, beta gamma subunits of heterotrimeric GTP-binding proteins, phospholipid cofactors, the calcium-binding proteins calmodulin and recoverin, posttranslational isoprenylation and palmitoylation, autophosphorylation, and protein kinase C-mediated GRK phosphorylation. Studies employing recombinant, purified proteins, cell culture, and transgenic animal models attest to the general importance of GRKs in regulating a vast array of GPCRs both in vitro and in vivo.
Howard Hughes Medical Institute, Department of Medicine (Cardiology), Duke University Medical Center, Durham, North Carolina 27710, USA. pitch001@mc.duke.edu
J A
JA
Pitcher
N J
NJ
Freedman
R J
RJ
Lefkowitz
D000494:Allosteric Regulation; D000818:Animals; D004194:Disease / Q000209:etiology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008322:Mammals; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity
D011956:Receptors, Cell Surface; D017346:Protein Serine-Threonine Kinases; D019204:GTP-Binding Proteins