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G-protein-coupled receptor regulation: role of G-protein-coupled receptor kinases and arrestins.

Publication ,  Journal Article
Ferguson, SS; Barak, LS; Zhang, J; Caron, MG
Published in: Can J Physiol Pharmacol
October 1996

G-protein-coupled receptors (GPCRs) represent a large family of proteins that transduce extracellular signals to the interior of cells. Signalling through these receptors rapidly desensitized primarily as the consequence of receptor phosphorylation, but receptor sequestration and downregulation can also contribute to this process. Two families of serine/threonine kinases, second messenger dependent protein kinases and receptor-specific G-protein-coupled receptor kinases (GRKs), phosphorylate GPCRs and thereby contribute to receptor desensitization. Receptor-specific phosphorylation of GPCRs promotes the binding of cytosolic proteins referred to as arrestins, which function to further uncouple GPCRs from their heterotrimeric G-proteins. To date, the GRK protein family consists of six members, which can be further classified into subgroups according to sequence homology and functional similarities. The arrestin protein family also comprises six members, which are subgrouped on the basis of sequence homology and tissue distribution. While the molecular mechanisms contributing to GPCR desensitization are fairly well characterized, little is known about the mechanism(s) by which GPCR responsiveness is reestablished, other than that receptor sequestration (internalization) might be involved. The goal of the present review is to overview current understanding of the regulation of GPCR responsiveness. In particular, we will review new evidence suggesting a pleiotropic role for GRKs and arrestins in the regulation of GPCR responsiveness. GRK-mediated phosphorylation and arrestin binding are not only involved in the functional uncoupling of GPCRs but they are also intimately involved in promoting GPCR sequestration and as such likely play an important role in mediating the subsequent resensitization of GPCRs.

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Published In

Can J Physiol Pharmacol

DOI

ISSN

0008-4212

Publication Date

October 1996

Volume

74

Issue

10

Start / End Page

1095 / 1110

Location

Canada

Related Subject Headings

  • Receptor Protein-Tyrosine Kinases
  • Physiology
  • Humans
  • GTP-Binding Proteins
  • Arrestin
  • Animals
  • 3214 Pharmacology and pharmaceutical sciences
  • 3208 Medical physiology
  • 1116 Medical Physiology
  • 1115 Pharmacology and Pharmaceutical Sciences
 

Citation

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Ferguson, S. S., Barak, L. S., Zhang, J., & Caron, M. G. (1996). G-protein-coupled receptor regulation: role of G-protein-coupled receptor kinases and arrestins. Can J Physiol Pharmacol, 74(10), 1095–1110. https://doi.org/10.1139/cjpp-74-10-1095
Ferguson, S. S., L. S. Barak, J. Zhang, and M. G. Caron. “G-protein-coupled receptor regulation: role of G-protein-coupled receptor kinases and arrestins.Can J Physiol Pharmacol 74, no. 10 (October 1996): 1095–1110. https://doi.org/10.1139/cjpp-74-10-1095.
Ferguson SS, Barak LS, Zhang J, Caron MG. G-protein-coupled receptor regulation: role of G-protein-coupled receptor kinases and arrestins. Can J Physiol Pharmacol. 1996 Oct;74(10):1095–110.
Ferguson, S. S., et al. “G-protein-coupled receptor regulation: role of G-protein-coupled receptor kinases and arrestins.Can J Physiol Pharmacol, vol. 74, no. 10, Oct. 1996, pp. 1095–110. Pubmed, doi:10.1139/cjpp-74-10-1095.
Ferguson SS, Barak LS, Zhang J, Caron MG. G-protein-coupled receptor regulation: role of G-protein-coupled receptor kinases and arrestins. Can J Physiol Pharmacol. 1996 Oct;74(10):1095–1110.

Published In

Can J Physiol Pharmacol

DOI

ISSN

0008-4212

Publication Date

October 1996

Volume

74

Issue

10

Start / End Page

1095 / 1110

Location

Canada

Related Subject Headings

  • Receptor Protein-Tyrosine Kinases
  • Physiology
  • Humans
  • GTP-Binding Proteins
  • Arrestin
  • Animals
  • 3214 Pharmacology and pharmaceutical sciences
  • 3208 Medical physiology
  • 1116 Medical Physiology
  • 1115 Pharmacology and Pharmaceutical Sciences