G Protein–Coupled Receptor Kinase
G protein–coupled receptor kinases (GRKs) represent a family of seven serine/threonine kinases that, based on their sequence similarities, can further be broken down into three subfamilies. These subfamilies include: GRK1, composed of GRK1 (rhodopsin kinase) and GRK7 (cone opsin kinase); GRK2, including GRK2 and GRK3; and GRK4, made up of GRK4, 5, and 6. These kinases were initially identified for their ability to phosphorylate G protein–coupled receptors (GPCRs). Phosphorylation of the receptor by GRKs leads to the recruitment of β-arrestins and consequently desensitization and internalization of the receptor. This internalization can then lead to additional signaling cascades. Furthermore, it has recently become evident that individual GRKs can interact in a kinase dependent or independent manner with nonreceptor substrates and influence a variety of physiological functions and pathologies.
Evolutionarily, GRKs are present in...
- Bownds D, Dawes J, Miller J, Stahlman M. Phosphorylation of frog photoreceptor membranes induced by light. Nature. 1972;237:125–7.Google Scholar
- Li L, Homan KT, Vishnivetskiy SA, Manglik A, Tesmer JJ, Gurevich VV, Gurevich EV. G protein-coupled receptor kinases of the GRK4 protein subfamily phosphorylate inactive G protein-coupled receptors (GPCRs). J Biol Chem. 2015;290(17):10775–90. https://doi.org/10.1074/jbc.M115.644773.CrossRefPubMedPubMedCentralGoogle Scholar