Ferguson Stephen S G
J. Allyn Centre for Cell Biology, Robarts Research Institute, 100 Perth Drive, PO Box 5015, London, Ontario N6A 5K8, Canada.
Trends Pharmacol Sci. 2007 Apr;28(4):173-9. doi: 10.1016/j.tips.2007.02.008. Epub 2007 Mar 9.
The uncoupling of G-protein-coupled receptors (GPCRs) from their cognate heterotrimeric G proteins provides an essential physiological 'feedback' mechanism that protects against both acute and chronic overstimulation of receptors. The primary mechanism by which GPCR activity is regulated is the feedback phosphorylation of activated GPCRs by kinases that are dependent on second messengers, GPCR kinases (GRKs) and arrestins. It has recently become apparent, however, that GRK2-mediated regulation of GPCR responsiveness also involves a phosphorylation-independent component that requires both heterotrimeric G-protein alpha-subunit interactions and GPCR binding. Moreover, in addition to GRK2, a growing number of GPCR-interacting proteins might contribute to the phosphorylation-independent G-protein uncoupling of GPCRs. Here, new information about the mechanisms underlying this phosphorylation-independent regulation of receptor and G-protein coupling is reviewed.
G蛋白偶联受体（GPCRs）与其同源异源三聚体G蛋白的解偶联提供了一种重要的生理“反馈”机制，可防止受体的急性和慢性过度刺激。调节GPCR活性的主要机制是依赖第二信使的激酶、GPCR激酶（GRKs）和抑制蛋白对活化的GPCR进行反馈磷酸化。然而，最近已经明确，GRK2介导的GPCR反应性调节还涉及一个不依赖磷酸化的成分，该成分需要异源三聚体G蛋白α亚基相互作用和GPCR结合。此外，除了GRK2，越来越多的与GPCR相互作用的蛋白质可能有助于GPCR不依赖磷酸化的G蛋白解偶联。本文综述了有关受体与G蛋白偶联的这种不依赖磷酸化调节机制的新信息。
