title: "Canonical and non-canonical actions of GRK5 in the heart".
abstract: As the average world-wide lifespan continues to increase, heart failure (HF) has dramatically increased in incidence leading to the highest degree of mortality and morbidity of any disease presently studied. G protein-coupled receptors (GPCRs) play a prominent role in regulation of cardiovascular function. GPCRs are effectively "turned off" by GPCR kinases (GRKs) in a process known as "desensitization". GRKs 2 and 5 are highly expressed in the heart, and known to be upregulated in HF. Over the last 20years, the role of GRK2 in HF has been widely studied. However, until recently, the role of GRK5 in cardiac pathophysiology had yet to be elucidated. In the present review, we will focus on GRK5's role in the myocardium in normal physiology, and its apparent critical role in the progression of HF. Further, we will also present potential therapeutic strategies (i.e. small molecule inhibition, gene therapy) that may have potential in combating the deleterious effects of GRK5 in HF.
authors.affiliation: Center for Translational Medicine, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, United States.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Traynham
authors.affiliation: Thomas Jefferson University, Philadelphia, PA 19107, United States.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hullmann
authors.affiliation: Center for Translational Medicine, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, United States. Electronic address: Walter.Koch@temple.edu.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
mesh_terms: D054774:G-Protein-Coupled Receptor Kinase 5 / Q000235:genetics* / Q000378:metabolism; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology
chemical_list: D054774:G-Protein-Coupled Receptor Kinase 5; C517898:GRK5 protein, human
keywords: G protein-coupled receptor; Heart failure; Hypertrophy; Myocardium
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