Regulatory effects of GRK2 on GPCRs and non-GPCRs and possible use as a drug target (Review)

  • Authors:
    • Chen-Chen Han
    • Yang Ma
    • Yifan Li
    • Yang Wang
    • Wei Wei
  • View Affiliations

  • Published online on: August 29, 2016     https://doi.org/10.3892/ijmm.2016.2720
  • Pages: 987-994
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Abstract

G protein-coupled receptor kinase 2 (GRK2) is a key member of the G protein-coupled receptor kinase (GRK) family. GRK2 activity is regulated by the C-terminus of GRK2 which contains a plekstrin homology domain and the N-terminus of GRK2 which contains the RGS homology domain with binding sites for several proteins and lipids such as G protein-coupled receptors (GPCRs), G protein, phospholipase C, phosphatidylinositol 4,5-bisphosphate, extracellular signal‑regulated kinase, protein kinase A and Gβγ. GRK2 phosphorylates the GPCR and enhances the affinity of binding to arrestins, which uncouple the receptors from G proteins, and target the receptors for desensitization and internalization. GRK2 also regulates non‑GPCR desensitization and internalization by phosphorylation, and is important in maintaining the balance between the receptors and signal transduction. Previous findings have indicated that the upregulation of GRK2 in heart failure enhances dysfunctional adrenergic signaling and myocyte death. Collagen-induced arthritis induces the upregulation of GRK2 expression in fibroblast-like synoviocytes. In this review, we discussed the evidence for the association between altered GRK2 levels and various diseases, which suggests that GRK2 may be an effective drug target for preventing and treating heart failure, hypertension and inflammatory disease.
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October-2016
Volume 38 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Han C, Ma Y, Li Y, Wang Y and Wei W: Regulatory effects of GRK2 on GPCRs and non-GPCRs and possible use as a drug target (Review). Int J Mol Med 38: 987-994, 2016
APA
Han, C., Ma, Y., Li, Y., Wang, Y., & Wei, W. (2016). Regulatory effects of GRK2 on GPCRs and non-GPCRs and possible use as a drug target (Review). International Journal of Molecular Medicine, 38, 987-994. https://doi.org/10.3892/ijmm.2016.2720
MLA
Han, C., Ma, Y., Li, Y., Wang, Y., Wei, W."Regulatory effects of GRK2 on GPCRs and non-GPCRs and possible use as a drug target (Review)". International Journal of Molecular Medicine 38.4 (2016): 987-994.
Chicago
Han, C., Ma, Y., Li, Y., Wang, Y., Wei, W."Regulatory effects of GRK2 on GPCRs and non-GPCRs and possible use as a drug target (Review)". International Journal of Molecular Medicine 38, no. 4 (2016): 987-994. https://doi.org/10.3892/ijmm.2016.2720