Potentiation of Rho-A-mediated lysophosphatidic acid activity by hyperinsulinemia
Potentiation of Rho-A-mediated lysophosphatidic acid activity by hyperinsulinemia
复制标题
DOI：
10.1074/jbc.m004798200
复制
发表时间：
2000-10-13
影响因子：
4.8
通讯作者：
Draznin, B
中科院分区：
文献类型：
--
作者：
Chappell, J;Golovchenko, I;Draznin, B
我们之前已经证明，胰岛素促进法呢基转移酶和香叶基香叶基转移酶 (GGTase) II 的磷酸化和激活。我们现在检查了胰岛素对 MCF-7 乳腺癌细胞中香叶基香叶基转移酶 I 的影响。胰岛素使 GGT 酶 I 活性增加 3 倍，并使香叶基香叶基化 Rho-A 的量增加 18%。胰岛素的这两种作用均被 GGT 酶 I 抑制剂 GGTI-286 阻断。胰岛素诱导的香叶基香叶基化 Rho-A 量增加导致 Rho-A 介导的溶血磷脂酸 (LPA) 对血清反应元件-荧光素酶构建体的作用增强。与单独的 LPA 相比，用胰岛素预孵育细胞将 LPA 刺激的血清反应元件荧光素酶激活增强至 1a 倍（p < 0.05）。胰岛素的增强作用呈剂量依赖性，可被 GGTI-286 抑制，但不会被胰岛素样生长因子-1 模拟。我们得出结论，胰岛素激活 GGT 酶 I，增加香叶基香叶基化 Rho-A 蛋白的量，并增强 MCF-7 乳腺癌细胞中 LPA 的 Rho-A 依赖性核效应。
We have shown previously that insulin promotes phosphorylation and activation of farnesyltransferase and geranylgeranyltransferase (GGTase) II. We have now examined the effect of insulin on geranylgeranyltransferase I in MCF-7 breast cancer cells. Insulin increased GGTase I activity 3-fold and augmented the amounts of geranylgeranylated Rho-A by 18%. Both effects of the insulin were blocked by an inhibitor of GGTase I, GGTI-286. The insulin-induced increases in the amounts of geranylgeranylated Rho-A resulted in potentiation of the Rho-A-mediated effects of lysophosphatidic acid (LPA) on a serum response element-luciferase construct. Preincubation of cells with insulin augmented the LPA-stimulated serum response element-luciferase activation to la-fold, compared with just g-fold for LPA alone (p < 0.05). The potentiating effect of insulin was dose-dependent, inhibited by GGTI-286 and not mimicked by insulin-like growth factor-1. We conclude that insulin activates GGTase I, increases the amounts of geranylgeranylated Rho-A protein, and potentiates the Rho-A-dependent nuclear effects of LPA in MCF-7 breast cancer cells.