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Insulin-like growth factor-1 induces the phosphorylation of PRAS40 via the PI3K/Akt signaling pathway in PC12 cells
Wang H.1; Zhang Q.1; Zhang L.1; Little P.J.3; Xie X.1; Meng Q.1; Ren Y.1; Zhou L.2; Gao G.2; Quirion R.4; Zheng W.1
2012-05-10
Source PublicationNeuroscience Letters
ISSN03043940 18727972
Volume516Issue:1Pages:105-109
AbstractInsulin-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. μM), 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. © 2012 Elsevier Ireland Ltd.
KeywordIGF-1 MAPK Neuronal cells survival PI3K/Akt PRAS40
DOI10.1016/j.neulet.2012.03.068
URLView the original
Language英語
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Cited Times [WOS]:17   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Zhongshan Ophthalmic Center
2.Sun Yat-Sen University, Zhongshan School of Medicine
3.RMIT University
4.McGill University, Douglas Mental Health University Institute
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GB/T 7714
Wang H.,Zhang Q.,Zhang L.,et al. Insulin-like growth factor-1 induces the phosphorylation of PRAS40 via the PI3K/Akt signaling pathway in PC12 cells[J]. Neuroscience Letters,2012,516(1):105-109.
APA Wang H..,Zhang Q..,Zhang L..,Little P.J..,Xie X..,...&Zheng W..(2012).Insulin-like growth factor-1 induces the phosphorylation of PRAS40 via the PI3K/Akt signaling pathway in PC12 cells.Neuroscience Letters,516(1),105-109.
MLA Wang H.,et al."Insulin-like growth factor-1 induces the phosphorylation of PRAS40 via the PI3K/Akt signaling pathway in PC12 cells".Neuroscience Letters 516.1(2012):105-109.
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