G蛋白偶联受体磷酸化研究进展

Advances in G protein-coupled receptor phosphorylation

G蛋白偶联受体(G protein-coupled receptors,GPCR)是具有重要生理病理功能的跨膜受体蛋白。GPCR磷酸化与G蛋白偶联受体激酶(G protein-coupled receptor kinases,GRKs)、蛋白激酶C(proteinkinase C,PKC)及β抑制蛋白(β-arrestin)密切相关。GPCR发生磷酸化可选择性的激活G蛋白依赖或G蛋白非依赖β-arresin信号转导通路,因而表现出偏向性受体/配体的特点。生物发光共振能量转移(bioluminescence resonance energy transfer,BRET)及Duolink等新技术的应用,推进了GPCR磷酸化的研究进程。本文简要综述了GRK、β-arrestin、PKC等对GPCR磷酸化的作用及GPCR发生磷酸化后对偏向性信号转导的影响,并探讨了目前研究GPCR磷酸化的最新技术,为进一步了解GPCR生理病理功能和药物研发提供理论基础。

G protein-coupled receptors （ GPCRs） are transmembrane proteins with important pathological and physiological functions.G protein-coupled receptor kinases （GRKs）,protein kinase C （PKC） and β-ar-restin are closely related to G protein-coupled receptor phosphorylation.The process of GPCR phosphoryla-tion selectively activates G protein-dependent or G-protein-independent signal transduction pathways,which shows the characteristics of the biased receptor/ligand.In addition, new technologies, such as biolumines-cence resonance energy transfer and Duolink etc.,furtherly promote the research of GPCRs phosphorylation. In this review,the effects of GRK,β-arrestin and PKC on the phosphorylation of GPCR and phosphorylation of GPCR were summarized.The application of newly found technologys in GPCR phosphorylation were also discussed,which provides a theoretical foundation to further understand GPCR physiological and pathological function and drug development.