Regulation of β-adrenergic receptor function
Regulation of β-adrenergic receptor function
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DOI：
10.4161/cc.10.21.18042
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发表时间：
2011-11
期刊：
影响因子：
4.3
通讯作者：
Neelakantan T. Vasudevan;M. Mohan;S. Goswami;S. N. Prasad
中科院分区：
文献类型：
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作者：
Neelakantan T. Vasudevan;M. Mohan;S. Goswami;S. N. Prasad
G蛋白偶联受体是调节多种细胞过程的细胞表面受体的最大家族。β-肾上腺素能受体（β-adrenergic receptor，βAR）是GPCR家族的典型成员，是研究最多的受体之一。βAR的激动剂激活导致构象变化，导致与G蛋白偶联，产生cAMP作为第二信使。激活的βAR被磷酸化，导致β-抑制蛋白结合，从而物理阻断G蛋白进一步偶联，导致受体脱敏。磷酸化的βAR被内化，并在早期内体中通过蛋白磷酸酶2A介导的去磷酸化进行再敏化。尽管脱敏和再敏化是维持受体稳态功能的同一枚硬币的两面，但人们对受体脱敏机制的理解却非常感兴趣，而对再敏化知之甚少。在我们目前的综述中，我们提供了对βAR功能调节的概述，特别强调受体再敏化及其在微调受体信号传导背景下的功能相关性。
G protein-coupled receptors are the largest family of cell surface receptors regulating multiple cellular processes. β-adrenergic receptor (βAR) is a prototypical member of GPCR family and has been one of the most well studied receptors in determining regulation of receptor function. Agonist activation of βAR leads to conformational change resulting in coupling to G protein generating cAMP as secondary messenger. The activated βAR is phosphorylated resulting in binding of β-arrestin that physically interdicts further G protein coupling leading to receptor desensitization. The phosphorylated βAR is internalized and undergoes resensitization by dephosphorylation mediated by protein phosphatase 2A in the early endosomes. Although desensitization and resensitization are two sides of the same coin maintaining the homeostatic functioning of the receptor, significant interest has revolved around understanding mechanisms of receptor desensitization while little is known about resensitization. In our current review we provide an overview on regulation of βAR function with a special emphasis on receptor resensitization and its functional relevance in the context of fine tuning receptor signaling.