Β-arrestin: a signaling molecule and potential therapeutic target for heart failure.

Β-arrestin: a signaling molecule and potential therapeutic target for heart failure.
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DOI:
10.1016/j.yjmcc.2010.11.005
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发表时间:
2011-10
影响因子:
5
通讯作者:
Rockman HA
Rockman HA
中科院分区:
医学2区
文献类型:
--
作者:
Noor N;Patel CB;Rockman HA

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目前,一些最有效的心力衰竭治疗靶向gpcr,如β -肾上腺素能受体(β1AR- β2AR)和血管紧张素II型IA受体(ATIaR)。这些受体的配体不仅通过阻断有害的G蛋白介导的导致心力衰竭的途径发挥作用,而且还通过G蛋白独立的途径发出信号,这些途径涉及G蛋白受体激酶(GRKs)的受体磷酸化,从而募集多功能蛋白β-阻滞蛋白。β-阻滞蛋白最初被认为在GPCR脱敏和内化中发挥作用,最近已被证明以一种通常对心脏具有保护作用的方式独立于经典第二信使介导信号。β-抑制蛋白的多功能性使其成为下一代心脏病药物开发中的一个有趣的分子,它有可能同时抑制有害的g蛋白依赖途径,同时激活有益的β-抑制蛋白介导的信号传导。在这篇综述中,我们探讨了β-抑制素信号传导的各个方面,并对其作为治疗心力衰竭的关键信号分子的潜在作用提出了看法。
Currently, some of the most effective treatments for heart failure target GPCRs such as the beta-adrenergic receptors (β1AR- β2AR) and angiotensin II type IA receptors (ATIaR). 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.
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