Differential regulation of insulin-stimulated tyrosine phosphorylation of IRS-1 and SHC by Wortmannin in intact cells.
Differential regulation of insulin-stimulated tyrosine phosphorylation of IRS-1 and SHC by Wortmannin in intact cells.
复制标题
完整细胞中渥曼青霉素对胰岛素刺激的 IRS-1 和 SHC 酪氨酸磷酸化的差异调节。
DOI：
10.1006/bbrc.1996.0849
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Goldstein,BJ
中科院分区：
文献类型：
--
作者：
Li,PM;Goldstein,BJ
Wortmannin 是磷脂酰肌醇 (PI) 3'-激酶的抑制剂，磷脂酰肌醇 (PI) 3'-激酶是一种通过与胰岛素受体底物-1 (IRS-1) 的磷酸酪氨酰残基对接而激活的细胞激酶，也可以在体外磷酸化 IRS-1 上的丝氨酸残基。用 100 nM 渥曼青霉素处理肝癌细胞后，响应胰岛素的 IRS-1 酪氨酸磷酸化增加了 38.3 ± 3.3%，而磷酸丝氨酸/苏氨酸含量降低19%。用 1 μM 渥曼青霉素处理进一步将 IRS-1 酪氨酸磷酸化增加到对照的 180%，而在这些条件下，IR 底物 p52 Shc 的酪氨酸磷酸化降低到对照的 50% 以下。因此，渥曼青霉素敏感激酶改变IR底物的丝氨酸磷酸化可以通过差异调节胰岛素刺激的酪氨酸磷酸化来调节胰岛素后受体信号传导途径。
Wortmannin is an inhibitor of phosphatidylinositol (PI) 3′-kinase, a cellular kinase activated by docking to phosphotyrosyl residues of insulin receptor substrate-1 (IRS-1) that can also phosphorylate serine residues on IRS-1in vitro.After treatment of hepatoma cells with 100 nM wortmannin, the tyrosine phosphorylation of IRS-1 in response to insulin was increased by 38.3 ± 3.3% while its phosphoserine/threonine content was reduced by 19%. Treatment with 1 μM wortmannin further increased IRS-1 tyrosine phosphorylation to 180% of control, while under these conditions, tyrosine phosphorylation of the IR substrate p52 Shc was reduced to less than 50% of control. Thus, alteration of the serine phosphorylation of IR substrates by a wortmannin-sensitive kinase may regulate post-insulin receptor signaling pathways by differential modulation of their insulin-stimulated tyrosine phosphorylation.