Issue Archive

[Research progress in signal bias of G protein-coupled receptor and its mechanism.] [Article in Chinese]

ZHAI Pei-Bin, MA Lan, LIU Xing^*

Pharmacology Research Center, Shanghai Medical College, Fudan University, Shanghai 200032, China

Abstract

G protein-coupled receptors (GPCRs) mediate signal transduction via G protein or β-arrestin. Several biased ligands and receptors that preferentially signal through either G protein- or β-arrestin-mediated pathways have been identified. These discoveries have redefined the classical GPCR signaling paradigm. Distinct ligand-receptor binding sites might be one of the main reasons for biased signal transduction. It is posited that multiple active conformations of receptors lead to distinct kinase phosphorylation patterns on C terminus of receptors. Phosphorylation patterns decide which signal pathway will be transduced. The biased signal pathway transduction has been found in more than 40 GPCRs till now. A few of them have been found involved in fine-regulation of physiological processes. However, most others still need further investigation. The biased ligands may be developed as tools for understanding the basic physiology of GPCR, and, potentially and most importantly, as fine-tuned therapeutics that maximize beneficial effects and minimize adverse or unwanted effects. These studies will provide new insights into new drug discovery.

Key words: G protein-coupled receptors; β-arrestin; biased GPCR signaling

Received: 2016-04-08　　Accepted: 2016-06-29

Corresponding author: 刘星　　E-mail: xingliu@fudan.edu.cn

Citing This Article：

ZHAI Pei-Bin, MA Lan, LIU Xing. [Research progress in signal bias of G protein-coupled receptor and its mechanism.] [Article in Chinese]. Acta Physiol Sin 2016; 68 (6): 790-798 (in Chinese with English abstract).