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lüll Beta-arrestin-mediated signaling in the heart Patel PA; Tilley DG; Rockman HACirc J 2008[Nov]; 72 (11): 1725-9Beta-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.|*MAP Kinase Signaling System[MESH]|Adrenergic beta-1 Receptor Agonists[MESH]|Animals[MESH]|Arrestins/*metabolism[MESH]|Chronic Disease[MESH]|Disease Models, Animal[MESH]|ErbB Receptors/agonists/metabolism[MESH]|Extracellular Signal-Regulated MAP Kinases/metabolism[MESH]|Heart Failure/drug therapy/metabolism[MESH]|Humans[MESH]|Myocardium/*metabolism[MESH]|Receptor, Angiotensin, Type 1/agonists/metabolism[MESH]|Receptors, Adrenergic, beta-1/metabolism[MESH]|beta-Arrestins[MESH] |