GRP94 promotes muscle differentiation by inhibiting the PI3K/AKT/mTOR signaling pathway
GRP94 promotes muscle differentiation by inhibiting the PI3K/AKT/mTOR signaling pathway
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GRP94通过抑制PI3K/AKT/mTOR信号通路促进肌肉分化
DOI：
10.1002/jcp.28727
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发表时间：
2019-11-01
影响因子：
5.6
通讯作者：
Yan, Yunqin
中科院分区：
文献类型：
--
作者：
Li, Shuang;Fu, Yuying;Yan, Yunqin
葡萄糖调节的内质网伴侣蛋白94（GRP 94）是许多生物过程所必需的，如免疫因子的分泌和中胚层诱导。在这里，我们证明了GRP 94在体外和体内促进肌肉分化。此外，GRP 94还能抑制PI 3 K/AKT/mTOR信号通路。使用体外和体内方法，在成肌细胞中，我们发现这种抑制导致增殖减少和分化增加。为了进一步研究GRP 94诱导肌肉分化的机制，我们使用免疫共沉淀和邻近连接试验，发现GRP 94与PI 3 K相互作用蛋白1（Pik 3 ip 1）相互作用。后一种蛋白通过抑制PI 3 K/AKT/mTOR途径促进肌肉分化。此外，发现GRP 94可以调节Pik 3 ip 1的表达。最后，当Pik 3 ip 1表达被抑制时，GRP 94诱导的肌肉分化促进作用减弱。综上所述，我们的数据表明，GRP 94促进肌肉分化，通过Pik 3 ip 1依赖性抑制PI 3 K/AKT/mTOR信号通路介导。
The glucose-regulated endoplasmic reticulum chaperone protein 94 (GRP94) is required for many biological processes, such as secretion of immune factors and mesoderm induction. Here, we demonstrated that GRP94 promotes muscle differentiation in vitro and in vivo. Moreover, GRP94 inhibited the PI3K/AKT/mTOR signaling pathway. Using both in vitro and in vivo approaches, in myoblasts, we found that this inhibition resulted in reduced proliferation and increased differentiation. To further investigate the mechanism of GRP94-induced muscle differentiation, we used co-immunoprecipitation and proximity ligation assays and found that GRP94 interacted with PI3K-interacting protein 1 (Pik3ip1). The latter protein promoted muscle differentiation by inhibiting the PI3K/AKT/mTOR pathway. Furthermore, GRP94 was found to regulate Pik3ip1 expression. Finally, when Pik3ip1 expression was inhibited, GRP94-induced promotion of muscle differentiation was diminished. Taken together, our data demonstrated that GRP94 promoted muscle differentiation, mediated by Pik3ip1-dependent inhibition of the PI3K/AKT/mTOR signaling pathway.