Specific activation of mGlu2 induced IGF-1R transactivation in vitro through FAK phosphorylation  

作　　者：Yong-jian Hu Qian Sun Wen-hua Zhang Yu-jia Huo Chan-juan Xu Jian-feng Liu 

机构地区：[1]Cellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China

出　　处：《Acta Pharmacologica Sinica》2019年第4期460-467,共8页中国药理学报（英文版）

基　　金：National Natural Science Foundation of China (NSFC grant nos. 31420103909, 31711530146, 31511130131);the Program of Introducing Talents of Discipline to the Universities of the Ministry of Education (grant no. B08029), Natural Science Foundation of.

摘　　要：Metabotropic glutamate receptor 2 (mGlu2) belongs to the group-ll metabotropic glutamate (mGlu) receptors and is a neurotransmitter G protein-coupled receptor. The group-ll mGlu receptors are promising antipsychotic targets, but the specific role of mGlu2 signaling remains unclear. Receptor tyrosine kinases (RTKs) are also believed to participate in brain pathogenesis. To in vestigate whether there is any communicatio n between mGlu2 and RTKs, we gen erated a CH0-mGlu2 cell li ne that stably expresses mGlu2 and showed that activation of mGlu2 by LY379268, a group II mGlu agonist, was able to transactivate insulin-like growth factor 1 receptor (IGF-1R). We further determined that the Gi/O protei n, GpY sub units, phospholipase C, and focal adhesion kinase (FAK) were involved in the IGF-1R transactivation signaling axis, which further induced the phosphorylation of extracellular sign al-regulated kinasei/2 (ERK1/2) and cAMP resp onse eleme nt-binding protei n. In primary mouse cortical neur ons, similar signaling pathways were observed when mGlu2 were stimulated by LY487379, an mGlu2 positive allosteric modulator. Transactivation of IGF-1R through FAK in response to mGlu2 should provide a better understanding of the association of mGlu2 with brain disease.

关 键 词：METABOTROPIC glutamate RECEPTOR 2 INSULIN-LIKE growth factor 1 RECEPTOR TRANSACTIVATION FAK ERK1/2 LY379268 LY487379 mouse cortical neurons 

分 类 号：R[医药卫生]