Beta-arrestin-mediated signaling in the heart.

Published

Journal Article (Review)

Beta-arrestin is a multifunctional adapter protein well known for its role in G-protein-coupled receptor (GPCR) desensitization. Exciting new evidence indicates that beta-arrestin is also a signaling molecule capable of initiating its own G-protein-independent signaling at GPCRs. One of the best-studied beta-arrestin signaling pathways is the one involving beta-arrestin-dependent activation of a mitogen-activated protein kinase cascade, the extracellular regulated kinase (ERK). ERK signaling, which is classically activated by agonist stimulation of the epidermal growth factor receptor (EGFR), can be activated by a number of GPCRs in a beta-arrestin-dependent manner. Recent work in animal models of heart failure suggests that beta-arrestin-dependent activation of EGFR/ERK signaling by the beta-1-adrenergic receptor, and possibly the angiotensin II Type 1A receptor, are cardioprotective. Hence, a new model of signaling at cardiac GPCRs has emerged and implicates classical G-protein-mediated signaling with promoting harmful remodeling in heart failure, while concurrently linking beta-arrestin-dependent, G-protein-independent signaling with cardioprotective effects. Based on this paradigm, a new class of drugs could be identified, termed "biased ligands", which simultaneously block harmful G-protein signaling, while also promoting cardioprotective beta-arrestin-dependent signaling, leading to a potential breakthrough in the treatment of chronic cardiac disease.

Full Text

Duke Authors

Cited Authors

  • Patel, PA; Tilley, DG; Rockman, HA

Published Date

  • November 2008

Published In

Volume / Issue

  • 72 / 11

Start / End Page

  • 1725 - 1729

PubMed ID

  • 18838825

Pubmed Central ID

  • 18838825

International Standard Serial Number (ISSN)

  • 1346-9843

Digital Object Identifier (DOI)

  • 10.1253/circj.cj-08-0734

Language

  • eng

Conference Location

  • Japan