title: The expanding GRK interactome: Implications in cardiovascular disease and potential for therapeutic development.
abstract: Heart failure (HF) is a global epidemic with the highest degree of mortality and morbidity of any disease presently studied. G protein-coupled receptors (GPCRs) are prominent regulators of cardiovascular function. Activated GPCRs are "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 20 years, both GRK2 and GRK5 have been demonstrated to be critical mediators of the molecular alterations that occur in the failing heart. In the present review, we will highlight recent findings that further characterize "non-canonical" GRK signaling observed in HF. Further, we will also present potential therapeutic strategies (i.e. small molecule inhibition, microRNAs, gene therapy) that may have potential in combating the deleterious effects of GRKs in HF.
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.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Traynham
authors.affiliation: Center for Translational Medicine, Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, United States.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Coleman
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: D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy; D006333:Heart Failure / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D035683:MicroRNAs / Q000627:therapeutic use; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D035683:MicroRNAs; D011943:Receptors, Adrenergic, beta; C496567:GRK2 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2; D054774:G-Protein-Coupled Receptor Kinase 5; C517898:GRK5 protein, human
keywords: G protein-coupled receptor; G protein-coupled receptor kinase; Heart failure; Hypertrophy; Myocardium