Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 46, Issue 3, Pages 300-308Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2008.11.015
Keywords
Beta-arrestin; G protein-coupled receptor; Signaling; Endocytosis; Trafficking; Desensitization; Beta-adrenergic receptor; Biased ligand; Transactivation; Angiotensinii type 1a receptor; Beta-blocker; Extracellular regulated kinase
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beta-arrestin1 and beta-arrestin2 were initially identified by sequence homology to visual arrestins and by their ability to bind to and inactivate signaling of the beta-2-adrenergic receptor in a process known as desensitization. While the role of beta-arrestins in desensitization has been known for some time, more recent evidence has revealed that beta-arrestins are multifunctional scaffolding proteins that are involved in numerous aspects of G protein-coupled receptor (GPCR) signaling. Interestingly, exciting new data shows that beta-arrestins can mediate signaling in their own right independent of classical second messenger mediated signaling, and that this beta-arrestin-mediated signaling may be cardioprotective. Identifying novel ligands for GPCRs that can block G protein-mediated signaling while simultaneously promoting beta-arrestin-mediated signaling could provide powerful new therapies for cardiac disease. (C) 2008 Elsevier Inc. All rights reserved.
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