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Insulin-like growth factor (IGF)-I regulates IGF-binding protein-5 gene expression through the phosphatidylinositol 3-kinase, protein kinase B/Akt, and p70 S6 kinase signaling pathway

我调整的像胰岛素的生长因素(IGF ) 通过 Phosphatidylinositol 3-Kinase,蛋白质 Kinase B/Akt,和 p70 S6 Kinase 的 IGF 有约束力的 Protein-5 基因表示发信号的小径

作     者:Duan, CM Liimatta, MB Bottum, OL 

作者机构:Univ Michigan Dept Biol Ann Arbor MI 48109 USA 

出 版 物:《JOURNAL OF BIOLOGICAL CHEMISTRY》 (生物化学杂志)

年 卷 期:1999年第274卷第52期

页      面:37147-37153页

核心收录:

学科分类:0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学] 

基  金:NIDDK NIH HHS [5P60DK-20572] Funding Source: Medline 

主  题:细胞 培养的 基因表达调控/药物作用 胰岛素样生长因子结合蛋白质5/遗传学 胰岛素样生长因子Ⅰ/药理学  平滑 血管/细胞学  平滑 血管/代谢 磷酸肌醇3-激酶类/生理学 蛋白质丝氨酸苏氨酸激酶 原癌基因蛋白质类/生理学 原癌基因蛋白质c-akt 视网膜母细胞瘤蛋白质/代谢 核糖体蛋白质S6激酶类/生理学  动物 

摘      要:Expression of the insulin-like growth factor-binding protein 5 (IGFBP-5) gene in vascular smooth muscle cells is up-regulated by IGF-I through an IGF-I receptor-mediated mechanism. In this study, we studied the possible involvement of the mitogen-activated protein kinase (MAPK) and PI 3-kinase signaling pathways in mediating IGF-I-regulated IGFBP-5 gene expression. The addition of Des(1-3)IGF-1, an IGF analog with reduced affinity to IGFBPs, resulted in a transient activation of p44 and p42 MAPK. Inhibition of the MAPK activation by PD98059, however, did not affect IGF-I-stimulated IGFBP-5 expression. Des(1-3)IGF-I treatment also strongly activated PI 3-kinase. This activation was probably mediated through IRS-1, because IGF-1 stimulation resulted in a significant increase in IRS-1- but not IRS-2-associated PI 3-kinase activity, This activation occurred within 5 min and was sustained at high levels for over 6 h. Likewise, Des(1-3)IGF-I caused a long lasting activation of PKB/Akt and p70(s6k). When LY294002 and wortmannin, two specific inhibitors of PI 3-kinase, were added with Des(1-3)IGF-I, the IGF-I-regulated IGFBP-5 expression was negated. The addition of rapamycin, which inhibits IGF-I-induced p70(s6k) activation, significantly inhibited IGF-I-regulated IGFBP-5 gene expression, These results suggest that the action of IGF-I on IGFBP-5 gene expression requires the activation of the PI 3-kinase-PKB/Akt-p70(s6k) pathway but not the MAPK pathway in vascular smooth muscle cells.

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