Metabotropic glutamate receptor 2 (mGlu2) belongs to the group-II metabotropic glutamate (mGlu) receptors and is a neurotransmitter G protein-coupled receptor. The group-II 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 investigate whether there is any communication between mGlu2 and RTKs, we generated a CHO-mGlu2 cell line 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 G_i/o protein, G_βγ subunits, phospholipase C, and focal adhesion kinase (FAK) were involved in the IGF-1R transactivation signaling axis, which further induced the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) and cAMP response element-binding protein. In primary mouse cortical neurons, 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.

中文翻译：

---

mGlu2的特异性激活通过FAK磷酸化在体外诱导了IGF-1R反式激活。

代谢型谷氨酸受体2（mGlu2）属于II类代谢型谷氨酸（mGlu）受体，是神经递质G蛋白偶联的受体。II组mGlu受体是有希望的抗精神病药物靶标，但mGlu2信号传导的具体作用仍不清楚。受体酪氨酸激酶（RTK）也被认为参与脑发病。为了研究mGlu2和RTK之间是否存在任何通讯，我们生成了稳定表达mGlu2的CHO-mGlu2细胞系，并显示II族mGlu激动剂LY379268激活了mGlu2，从而能够激活胰岛素样生长因子1受体。 （IGF-1R）。我们进一步确定了G _{i / o}蛋白_Gβγ亚基，磷脂酶C和粘着斑激酶（FAK）参与了IGF-1R反式激活信号转导轴，进一步诱导了细胞外信号调节激酶1/2（ERK1 / 2）和cAMP反应元件结合蛋白的磷酸化。在原代小鼠皮层神经元中，当mGlu2被mGlu2阳性变构调节剂LY487379刺激时，观察到类似的信号通路。通过FAK对mGlu2进行IGF-1R的反式激活，应该可以更好地了解mGlu2与脑疾病的关系。