beta-Arrestin: A signaling molecule and potential therapeutic target for heart failure

Duke University School of Medicine, Durham, NC, USA.
Journal of Molecular and Cellular Cardiology (Impact Factor: 5.22). 11/2010; 51(4):534-41. DOI: 10.1016/j.yjmcc.2010.11.005
Source: PubMed

ABSTRACT Currently, some of the most effective treatments for heart failure target GPCRs such as the beta-adrenergic receptors (β1AR and β2AR) and angiotensin II type IA receptors (AT1aR). Ligands for these receptors not only function by blocking the deleterious G-protein mediated pathway leading to heart failure, but also signal via G-protein independent pathways that involve receptor phosphorylation by G-protein receptor kinases (GRKs) leading to recruitment of the multifunctional protein, β-arrestin. Originally thought to play a role in GPCR desensitization and internalization, β-arrestin has recently been shown to mediate signaling independent of classical second messengers in a way that is often protective to the heart. The multi-functionality of β-arrestin makes it an intriguing molecule in the development of the next generation of drugs for cardiac diseases with the potential to simultaneously inhibit deleterious G-protein dependent pathways while activating beneficial β-arrestin mediated signaling. In this review, we explore various facets of β-arrestin signaling and offer a perspective on its potential role as a key signaling molecule in the treatment of heart failure. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."

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