Sato Priscila Y, Chuprun J Kurt, Schwartz Mathew, Koch Walter J
Center for Translational Medicine and Department of Pharmacology, Temple University School of Medicine, Philadelphia, Pennsylvania; and Advanced Institutes of Convergence Technology, Suwon, South Korea.
Physiol Rev. 2015 Apr;95(2):377-404. doi: 10.1152/physrev.00015.2014.
G protein-coupled receptors (GPCRs) are important regulators of various cellular functions via activation of intracellular signaling events. Active GPCR signaling is shut down by GPCR kinases (GRKs) and subsequent β-arrestin-mediated mechanisms including phosphorylation, internalization, and either receptor degradation or resensitization. The seven-member GRK family varies in their structural composition, cellular localization, function, and mechanism of action (see sect. II). Here, we focus our attention on GRKs in particular canonical and novel roles of the GRKs found in the cardiovascular system (see sects. III and IV). Paramount to overall cardiac function is GPCR-mediated signaling provided by the adrenergic system. Overstimulation of the adrenergic system has been highly implicated in various etiologies of cardiovascular disease including hypertension and heart failure. GRKs acting downstream of heightened adrenergic signaling appear to be key players in cardiac homeostasis and disease progression, and herein we review the current data on GRKs related to cardiac disease and discuss their potential in the development of novel therapeutic strategies in cardiac diseases including heart failure.
G蛋白偶联受体（GPCRs）通过激活细胞内信号转导事件，成为各种细胞功能的重要调节因子。GPCR激酶（GRKs）以及随后由β-抑制蛋白介导的机制（包括磷酸化、内化以及受体降解或再敏化）可关闭GPCR的活性信号。GRK七成员家族在其结构组成、细胞定位、功能及作用机制方面存在差异（见第二节）。在此，我们将重点关注GRKs，特别是在心血管系统中发现的GRKs的典型和新作用（见第三节和第四节）。对整体心脏功能至关重要的是由肾上腺素能系统提供的GPCR介导的信号转导。肾上腺素能系统的过度刺激与包括高血压和心力衰竭在内的各种心血管疾病病因密切相关。作用于增强的肾上腺素能信号下游的GRKs似乎是心脏稳态和疾病进展的关键参与者，在此我们回顾了目前关于与心脏病相关的GRKs的数据，并讨论它们在包括心力衰竭在内的心脏病新型治疗策略开发中的潜力。
