GRK2: multiple roles beyond G protein-coupled receptor desensitization

Trends Pharmacol Sci. 2012 Mar;33(3):154-64. doi: 10.1016/ Epub 2012 Jan 23.


G protein-coupled receptor kinases (GRKs) regulate numerous G protein-coupled receptors (GPCRs) by phosphorylating the intracellular domain of the active receptor, resulting in receptor desensitization and internalization. GRKs also regulate GPCR trafficking in a phosphorylation-independent manner via direct protein-protein interactions. Emerging evidence suggests that GRK2, the most widely studied member of this family of kinases, modulates multiple cellular responses in various physiological contexts by either phosphorylating non-receptor substrates or interacting directly with signaling molecules. In this review, we discuss traditional and newly discovered roles of GRK2 in receptor internalization and signaling as well as its impact on non-receptor substrates. We also discuss novel exciting roles of GRK2 in the regulation of dopamine receptor signaling and in the activation and trafficking of the atypical GPCR, Smoothened (Smo).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • G-Protein-Coupled Receptor Kinase 2 / metabolism*
  • Humans
  • Phosphorylation
  • Receptors, Dopamine / metabolism*
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction


  • Receptors, Dopamine
  • Receptors, G-Protein-Coupled
  • G-Protein-Coupled Receptor Kinase 2