Insulin-like growth factor-1 induces the phosphorylation of PRAS40 via the PI3K/Akt signaling pathway in PC12 cells

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• 作者：Haitao Wang^a ; ¹ ; Qishan Zhang^a ; ¹ ; Lang Zhang^a ; Peter J. Little^b ; Xiaochun Xie^a ; Qian Meng^a ; Yannan Ren^a ; Lihua Zhou^d ; Guoquan Gao^d ; Remi Quirion^c ; Wenhua Zheng^a ; ^{whzheng123@gmail.com}
• 关键词：IGF-1 ; PRAS40 ; PI3K/Akt ; MAPK ; Neuronal cells survival
• 刊名：Neuroscience Letters
• 出版年：2012
• 期刊代码：52_03043940
• 类别：neu
• 出版时间：10 May, 2012
• 卷：516
• 期：1
• 页码：105-109
• 文件大小：585 K

摘要

Insulin-like growth factor-1 (IGF-1) is a polypeptide tropic factor that plays an important role in the survival and differentiation of both neuronal and non-neuronal cells. Numerous studies have demonstrated that IGF-1 promotes neuronal cell survival via the PI3K/Akt signaling pathway. Proline-rich Akt substrate of 40 kDa (PRAS40) is a recently discovered downstream target of Akt. However, the relationship between IGF-1 and PRAS40 is not known. In this study, we characterized the phosphorylation of PRAS40 induced by IGF-1 in PC12 cells and explored the signaling pathway responsible for the effect of IGF-1. IGF-1 induced the phosphorylation of Akt at Thr473 and PRAS40 at Thr246 in PC12 cells. The phosphorylation of Akt and PRAS40 induced by IGF-1 (100 ng/ml) was inhibited by the phosphatidylinositide 3-kinase (PI3K) specific inhibitor LY294002 (50 渭M), while no inhibitory effect was observed for a MAPK kinase pathway specific inhibitor PD98059 nor a p38 MAPK inhibitor PD169316, suggesting that the phosphorylation of PRAS40 induced by IGF-1 is mediated by the PI3K pathway in PC12 cells and primary cultured neurons. In further support this hypothesis, an Akt kinase specific inhibitor, Akt inhibitor VIII, attenuated IGF-1-induced phosphorylation of PRAS40 at the concentration that blocked the phosphorylation of Akt induced by IGF-1. Taken together, these data demonstrate that IGF-1 stimulates the phosphorylation of PRAS40 at Thr246 in neuronal cells and the effect of IGF-1 is mediated, at least in part, by the PI3K/Akt signaling pathway.