G protein coupled receptor kinases as therapeutic targets in cardiovascular disease.
G protein coupled receptor kinases as therapeutic targets in cardiovascular disease.
复制标题
DOI：
10.1161/circresaha.110.231233
复制
发表时间：
2011-07-22
影响因子：
20.1
通讯作者：
Blaxall BC
中科院分区：
文献类型：
--
作者：
Belmonte SL;Blaxall BC
G蛋白偶联受体(GPCRs)是最大的膜受体家族，负责调节多种生理过程。这是通过配体与GPCRs结合，激活相关的异源三聚体G蛋白和细胞内信号通路来实现的。G蛋白偶联受体激酶(GRKs)与β-arrestins一起，经典地使受体信号转导脱敏，从而阻止GPCR第二信使级联的过度激活。随着GRK表达的改变在许多心血管疾病中的显著表现，包括心力衰竭、心肌梗死、高血压和心肌肥厚，GRK作为潜在的诊断或治疗靶点已被广泛研究。在这里，我们回顾了我们对GRKs在心血管病理生理学中的作用的不断发展的理解。
G protein-coupled receptors (GPCRs) represent the largest family of membrane receptors and are responsible for regulating a wide variety of physiological processes. This is accomplished via ligand binding to GPCRs, activating associated heterotrimeric G proteins and intracellular signaling pathways. G protein-coupled receptor kinases (GRKs), in concert with β-arrestins, classically desensitize receptor signal transduction, thus preventing hyperactivation of GPCR second messenger cascades. As changes in GRK expression have featured prominently in many cardiovascular pathologies, including heart failure, myocardial infarction, hypertension, and cardiac hypertrophy, GRKs have been intensively studied as potential diagnostic or therapeutic targets. Herein, we review our evolving understanding of the role of GRKs in cardiovascular pathophysiology.