Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Circ Res. 2011 Jul 22;109(3):309-19. doi: 10.1161/CIRCRESAHA.110.231233.
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.
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 GPCR 结合，激活相关的异三聚体 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 协同作用，经典地使受体信号转导脱敏，从而防止 GPCR 第二信使级联的过度激活。由于 GRK 表达的变化在许多心血管疾病中表现得尤为突出，包括心力衰竭、心肌梗死、高血压和心肌肥厚，因此 GRKs 已被深入研究为潜在的诊断或治疗靶点。本文综述了我们对 GRKs 在心血管病理生理学中作用的不断认识。
