The expanding GRK interactome: Implications in cardiovascular disease and potential for therapeutic development. (August 2016)

• Record Type: Journal Article
• Authors: Hullmann, Jonathan; Traynham, Christopher J.; Coleman, Ryan C.; Koch, Walter J.
• Is Part Of: Pharmacological research. Volume 110(2016:Aug.)
• Page Start: 52
• Page End: 64
• Publication Date: 2016-08
• Subjects: 3′ UTR 3′ untranslated region -- AAV6 adeno-associated virus serotype 6 -- Ad adenoviral -- AT1R angiotension receptor -- AR adrenergic receptor -- AngII angiotensin II -- C carboxyl -- Ca2+ calcium -- CaM calmodulin -- CSQ calseqestrin -- DCM dilated cardiomyopathy -- EGFR epidermal growth factor -- eNOS endothelial nitric oxide synthase -- GPCR G protein-coupled receptor -- GRK G protein-coupled receptor kinase -- GRK2-C340S mice wherein GRK2 cannot be S-nitrosylated -- GRK5-NLS mice wherein GRK5 cannot be targeted to the nucleus -- HDAC histone deacetylase -- Hsp90 heat shock protein 90 -- HF heart failure -- I/R ischemia-reperfusion -- KO knockout -- LV left ventricular -- MEF2 myocyte enhancer factor 2 -- MI myocardial infarction -- MLP muscle lim protein -- NLS nuclear localization sequence -- NO nitric oxide -- NOX-4 NADPH oxidase-4 -- RGS regulator of G protein signaling -- RH region of homology -- ROS reactive oxygen species -- SNS sympathetic nervous system -- SSRI serotonin reuptake inhibitor -- TAC transverse aortic constriction -- TgGRK5 transgenic GRK5; G protein-coupled receptor -- G protein-coupled receptor kinase -- Hypertrophy -- Heart failure -- Myocardium; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2016.05.008
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: 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.