Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

G Protein–Coupled Receptor Kinase

  • Michael Steury
  • Narayanan Parameswaran
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101633

Synonyms

Historical Background

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...

This is a preview of subscription content, log in to check access.

References

  1. Benovic JL, DeBlasi A, Stone WC, Caron MG, Lefkowitz RJ. Beta-adrenergic receptor kinase: primary structure delineates a multigene family. Science. 1989;246:235–40.PubMedCrossRefGoogle Scholar
  2. Benovic JL, Strasser RH, Caron MG, Lefkowitz RJ. Beta-adrenergic receptor kinase: identification of a novel protein kinase that phosphorylates the agonist-occupied form of the receptor. Proc Natl Acad Sci USA. 1986;83:2797–801.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Bownds D, Dawes J, Miller J, Stahlman M. Phosphorylation of frog photoreceptor membranes induced by light. Nature. 1972;237:125–7.Google Scholar
  4. Buczylko J, Gutmann C, Palczewski K. Regulation of rhodopsin kinase by autophosphorylation. Proc Natl Acad Sci USA. 1991;88(6):2568–72.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Gainetdinov RR, Premont RT, Bohn LM, Lefkowitz RJ, Caron MG. Desensitization of G protein-coupled receptors and neuronal functions. Annu Rev Neurosci. 2004;27:107–44.PubMedCrossRefGoogle Scholar
  6. Gurevich EV, Tesmer JJ, Mushegian A, Gurevich VV. G protein-coupled receptor kinases: more than just kinases and not only for GPCRs. Pharmacol Ther. 2012;133:40–69.PubMedCrossRefGoogle Scholar
  7. Gurevich VV, Gurevich EV. G protein-coupled receptor kinases (GRKs) history: evolution and discovery. In: Gurevich VV, Gurevich EV, Tesmer J, editors. G protein-coupled receptor kinases. Springer: New York; 2016. p. 3–22.CrossRefGoogle Scholar
  8. Inglese J, Freedman NJ, Koch WJ, Lefkowitz RJ. Structure and mechanism of the G protein-coupled receptor kinases. J Biol Chem. 1993;268(32):23735–8.PubMedGoogle Scholar
  9. Inglese J, Koch WJ, Caron MG, Lefkowitz RJ. Isoprenylation in regulation of signal transduction by G-protein-coupled receptor kinases. Nature. 1992;359(6391):147–50.PubMedCrossRefGoogle Scholar
  10. Jaber M, Koch WJ, Rockman H, Smith B, Bond RA, Sulik KK, Ross Jr J, Lefkowitz RJ, Caron MG, Giros B. Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function. Proc Natl Acad Sci USA. 1996;93:12974–9.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Krupnick JG, Gurevich VV, Benovic JL. Mechanism of quenching of photo- transduction. Binding competition between arrestin and transducin for phosphorhodopsin. J Biol Chem. 1997;272(29):18125–31.PubMedCrossRefGoogle Scholar
  12. 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
  13. Orban T, Palczewski K. Structure and function of G-protein-coupled receptor kinases 1 and 7. In: Gurevich VV, Gurevich EV, Tesmer J, editors. G protein-coupled receptor kinases. Springer: New York; 2016. p. 25–43.CrossRefGoogle Scholar
  14. Packiriswamy N, Parameswaran N. G-protein-coupled receptor kinase in inflammation and disease. Genes Immun. 2015;16:367–77.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Pitcher J, Freedman N, Lefkowitz RJ. G protein-coupled receptor kinases. Annu Rev Biochem. 1998;67:653–92.PubMedCrossRefGoogle Scholar
  16. Premont RT, Gainetdinov RR. Physiological roles of G protein-coupled receptor kinases and arrestins. Annu Rev Physiol. 2007;69:511–34.PubMedCrossRefGoogle Scholar
  17. Premont RT, Macrae AD, Aparicio SA, Kendall HE, Welch JE, Lefkowitz RJ. The GRK4 subfamily of G protein-coupled receptor kinases: alternative splicing, gene organization, and sequence conservation. J Biol Chem. 1999;274(41):29381–9.PubMedCrossRefGoogle Scholar
  18. Ribas C, Penela P, Murga C, Salcedo A, Garcia-Hoz C, Jurado-Pueyo M, Aymerich I, Mayor F. The G protein-coupled receptor kinase (GRK) interactome: role of GRKs in GPCR regulation and signaling. Biochim Biophys Acta. 2007;1768:913–22.PubMedCrossRefGoogle Scholar
  19. Sato PY, Chuprun JK, Schwartz M, Koch WJ. The evolving impact of G protein-coupled receptor kinases in cardiac health and disease. Physiol Rev. 2015;95(2):377–404.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Xu H, Jiang X, Shen K, Fischer CC, Wedegaertner PB. The regulator of G protein signaling (RGS) domain of G protein- coupled receptor kinase 5 (GRK5) regulates plasma membrane localization and function. Mol Biol Cell. 2014;25(13):2105–15.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of PhysiologyMichigan State UniversityEast LansingUSA