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

• DOI: 10.1016/j.neulet.2012.03.068
• Publication Date: 2012-04-03T18:02:39Z
• Authors: Haitao Wang; Qishan Zhang; Lang Zhang; Peter J. Little; Xiaochun Xie; Qian Meng; Yannan Ren; Lihua Zhou; Guoquan Gao; Remi Quirion; Wenhua Zheng
• Keywords: 2800 Neuroscience; PI3K/Akt; 0303 health sciences; PRAS40; Adenylate Kinase; Neuronal cells survival; MAPK; PC12 Cells; Rats; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; 616; IGF-1; Animals; Insulin-Like Growth Factor I; Phosphorylation; Adaptor Proteins, Signal Transducing; Signal Transduction

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 40kDa (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 (100ng/ml) was inhibited by the phosphatidylinositide 3-kinase (PI3K) specific inhibitor LY294002 (50μM), 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.