Department of Pharmaceutical Sciences, Nova Southeastern University College of Pharmacy, Ft. Lauderdale, FL 33328, USA.
Pharmacogenomics. 2012 Feb;13(3):323-41. doi: 10.2217/pgs.11.178.
Heptahelical G-protein-coupled receptors are the most diverse and therapeutically important family of receptors, playing major roles in the physiology of various organs and tissues. They couple their ligand binding to G-protein activation, which then transmits intracellular signals. G-protein signaling is terminated by phosphorylation of the receptor by the family of G-protein-coupled receptor kinases (GRKs), followed by arrestin (Arr) binding, which uncouples the phosphorylated receptor from the G-protein and subsequently targets the receptor for internalization. Moreover, Arrs can transmit signals in their own right during receptor internalization. Genetic polymorphisms in receptors, as well as in GRK and Arr family members per se, which affect regulation of receptor signaling and function, have just started being identified and characterized. The present review will discuss what is known so far in this evolving field of GRK/Arr pharmacogenomics, as well as highlight important areas likely to produce invaluable information in the future.
七次跨膜 G 蛋白偶联受体是最多样化和最重要的受体家族，在各种器官和组织的生理学中发挥主要作用。它们将配体结合与 G 蛋白激活偶联，从而传递细胞内信号。G 蛋白信号通过 G 蛋白偶联受体激酶 (GRK) 家族对受体的磷酸化来终止，随后与 arrestin (Arr) 结合，将磷酸化的受体与 G 蛋白解偶联，并随后将受体靶向内化。此外，Arr 在受体内化过程中本身可以传递信号。受体、GRK 和 Arr 家族成员本身中的遗传多态性，影响受体信号转导和功能的调节，刚刚开始被识别和表征。本综述将讨论在这个不断发展的 GRK/Arr 药物基因组学领域中迄今为止所了解的情况，并强调未来可能产生宝贵信息的重要领域。
