title: Insulin-like growth factor-1 induces the phosphorylation of PRAS40 via the PI3K/Akt signaling pathway in PC12 cells.
abstract: 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.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center and Neurophamacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guanzhou, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Wang
authors.forename: Qishan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Lang
authors.initials: L
authors.lastname: Zhang
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Little
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Xie
authors.forename: Qian
authors.initials: Q
authors.lastname: Meng
authors.forename: Yannan
authors.initials: Y
authors.lastname: Ren
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhou
authors.forename: Guoquan
authors.initials: G
authors.lastname: Gao
authors.forename: Remi
authors.initials: R
authors.lastname: Quirion
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C516104:Akt1s1 protein, rat; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D000263:Adenylate Kinase; C110938:adenylate kinase 2