The evolving impact of g protein-coupled receptor kinases in cardiac health and disease

Physiol Rev. 2015 Apr;95(2):377-404. doi: 10.1152/physrev.00015.2014.


G protein-coupled receptors (GPCRs) are important regulators of various cellular functions via activation of intracellular signaling events. Active GPCR signaling is shut down by GPCR kinases (GRKs) and subsequent β-arrestin-mediated mechanisms including phosphorylation, internalization, and either receptor degradation or resensitization. The seven-member GRK family varies in their structural composition, cellular localization, function, and mechanism of action (see sect. II). Here, we focus our attention on GRKs in particular canonical and novel roles of the GRKs found in the cardiovascular system (see sects. III and IV). Paramount to overall cardiac function is GPCR-mediated signaling provided by the adrenergic system. Overstimulation of the adrenergic system has been highly implicated in various etiologies of cardiovascular disease including hypertension and heart failure. GRKs acting downstream of heightened adrenergic signaling appear to be key players in cardiac homeostasis and disease progression, and herein we review the current data on GRKs related to cardiac disease and discuss their potential in the development of novel therapeutic strategies in cardiac diseases including heart failure.

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
  • G-Protein-Coupled Receptor Kinase 5 / metabolism
  • G-Protein-Coupled Receptor Kinases / metabolism*
  • Heart Diseases / enzymology*
  • Heart Diseases / physiopathology
  • Humans
  • Myocardium / enzymology*
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction*


  • Receptors, G-Protein-Coupled
  • G-Protein-Coupled Receptor Kinase 2
  • G-Protein-Coupled Receptor Kinase 5
  • G-Protein-Coupled Receptor Kinases