Mechanisms of β-arrestin-biased GPCR signal transduction and advances in drug research
10.16438/j.0513-4870.2018-0610
- VernacularTitle:偏向β-抑制蛋白的GPCR信号传导机制及药物研究进展
- Author:
Lin YIN
1
;
Xi CHEN
1
;
Xiu-ying YANG
1
;
Guan-hua DU
1
Author Information
1. Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
G protein-coupled receptor;
italic>β-arrestin;
mechanism of bias;
bias calculation method;
biased ligand drug
- From:
Acta Pharmaceutica Sinica
2019;54(1):66-72
- CountryChina
- Language:Chinese
-
Abstract:
G protein-coupled receptors (GPCR) are a class of receptor superfamily that exist on the surface of cell membrane. With the intensive studies on the GPCR desensitization regulator—β-arrestins, it is found that activated GPCR can not only conduct signal transduction through G protein-dependent pathway, but also mediate via non-G protein-dependent pathway. In addition to mediate endocytosis and desensitization, β-arrestins also initiate a new series of signal transduction events. Therefore, the concept of "biased transduction" was put forward: the receptor activated by a specific ligand could selectively activate a specific signaling pathway, leading the signal to be transmitted downstream along a "preferential" pathway. We call the ligand that binds to the receptor and causes biased activation "biased ligand". It is generally believed that the phenomenon of bias results from different binding modes of ligands and receptors, including multiple receptor conformations, diverse sites that downstream signal proteins bind, and signal proteins’ own conformations, etc. Here we give a brief review focusing on the mechanisms of β-arrestin-biased GPCR signal transduction and the advances in the drug development on β-arrestin biased ligands.
