Beta-Arrestin-Mediated Signaling in the Heart

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概要

• 論文の詳細を見る

• Beta-arrestin is a multifunctional adapter protein well known for its role in G-protein-coupled receptor (GPCR) desensitization. Exciting new evidence indicates that β-arrestin is also a signaling molecule capable of initiating its own G-protein-independent signaling at GPCRs. One of the best-studied β-arrestin signaling pathways is the one involving β-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 β-arrestin-dependent manner. Recent work in animal models of heart failure suggests that β-arrestin-dependent activation of EGFR/ERK signaling by the β-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 β-arrestin-dependent, G-protein-inde-pendent 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 β-arrestin-dependent signaling, leading to a potential breakthrough in the treatment of chronic cardiac disease.

• 社団法人日本循環器学会の論文
• 2008-10-20

著者

• Rockman Howard

  Department Of Cell Biology And Genetics Duke University

• Tilley Douglas

  Department Of Medicine Duke University

• Patel Priyesh

  School of Medicine, Duke University

• Patel Priyesh

  School Of Medicine Duke University

関連論文

• Genetic Modifier Loci Affecting Survival and Cardiac Function in Murine Dilated Cardiomyopathy
• Beta-Arrestin-Mediated Signaling in the Heart

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