کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2190827 | 1097821 | 2011 | 8 صفحه PDF | دانلود رایگان |

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.”
Research Highlights
► β-arrestin is known to mediate GPCR desensitization and trafficking.
► β-arrestin has now been shown to activate signaling independent of signaling.
► β-arrestin mediated signaling is cardioprotective.
► Identifying ligands that trigger β-arrestin signaling may lead to a new generation of drugs to treat heart failure.
Journal: Journal of Molecular and Cellular Cardiology - Volume 51, Issue 4, October 2011, Pages 534–541