Non-visual GRKs: are we seeing the whole picture?

• Published in: Trends in pharmacological sciences (Regular ed.) Vol. 24; no. 12; pp. 626 - 633
• Main Authors: Willets, Jonathon M., Challiss, R.A.John, Nahorski, Stefan R.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2003
• Subjects: Animals; Humans; Phosphorylation; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - metabolism; Protein-Serine-Threonine Kinases - physiology; Receptors, G-Protein-Coupled - metabolism; Receptors, G-Protein-Coupled - physiology; Signal Transduction
• ISSN: 0165-6147; 1873-3735
• DOI: 10.1016/j.tips.2003.10.003

G-protein-coupled receptor kinases (GRKs) comprise a family of seven mammalian serine/threonine protein kinases that phosphorylate and regulate agonist-occupied or constitutively active G-protein-coupled receptors (GPCRs). Studies of the details and consequences of these mechanisms have focused heavily on the original β-adrenoceptor kinase (β-ARK) family (GRK2 and GRK3) and, in particular, on phosphorylation-dependent recruitment of adaptor proteins such as the β-arrestins. However, recent work has indicated roles for the other, non-visual GRKs (GRK4, GRK5 and GRK6) and has revealed potential phosphorylation-independent regulation of GPCRs by GRK2 and GRK3. In this article, we review this newer information and attempt to put it into context with GRKs as physiological regulators that could be appropriate targets for future pharmacological intervention.