G蛋白偶联受体激酶的调控

Regulation of G Protein-coupled Receptor Kinase

G蛋白偶联受体激酶(Gprotein-coupledreceptorkinase,GRK)特异地使活化的G蛋白偶联受体(Gprotein-coupledreceptor,GPCR)发生磷酸化及脱敏化,从而终止后者介导的信号转导通路。研究表明,GRK的功能被高度调控,并具有下行调节GPCR的能力。调控GRK功能的机制包括两个层次:(1)多种途径调控激酶的亚细胞定位及活性,包括GPCR介导、G蛋白偶联、磷脂作用、Ca2+结合蛋白调控、蛋白激酶C活化、MAPK反馈抑制、小窝蛋白抑制等;(2)调控GRK表达水平,主要体现在其与某些疾病的联系。

G protein-coupled receptor kinase (GRK) specifically phosphorylate the agonist-activated form of G protein-coupled receptor (GPCR), raising its desensitization and then terminating the GPCR-induced signaling. Upon the discovery of GRK family since mid-1980s, it's desired for understanding the biochemical and molecular mechanism of regulation of the GPCR responsiveness. Recent studies demonstrated that the function of GRK is highly regulated, and in this manner regulates the responsiveness of GPCR, among those seven have been identified. The regulating mechanism of the GRK function could be understood in two aspects: (1) subcellular localization and the regulation of GRK kinase activity, including the interaction with GPCR, G protein, phospholipids, Ca2+-binding protein, PKC, MAPK, and caveolin; (2) the regulation of GRK expression level in correlation with some diseases, such as cardiovascular disease, hypertension, and inflammation.