Akt介导的糖原合成酶激酶-3β抑制作用通过Rac1阻止多胺缺乏的肠上皮细胞迁移。
Akt-mediated GSK-3beta inhibition prevents migration of polyamine-depleted intestinal epithelial cells via Rac1.
作者信息
Vaidya R J, Ray R M, Johnson L R
机构信息
Department of Physiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
出版信息
Cell Mol Life Sci. 2006 Dec;63(23):2871-9. doi: 10.1007/s00018-006-6379-x.
The rapid migration of intestinal epithelial cells (IEC) is important for the healing of mucosal wounds. We have previously shown that polyamine depletion inhibits migration of IEC-6 cells. Akt activation and its downstream target GSK-3beta have been implicated in the regulation of migration. Here we investigated the significance of elevated phosphatidylinositol 3-kinase (PI3K)/Akt signaling on migration of polyamine-depleted cells. Polyamine-depleted cells had high Akt (Ser473) and GSK-3beta (Ser9) phosphorylation. Pretreatment with 20 microM LY294002 (PI3K inhibitor) for 30 min inhibited phosphorylation of Akt, increased migration by activating Rac1 in polyamine-depleted IEC-6 cells, and restored the actin structure similar to that in cells grown in control medium. Treatment of cells with a GSK-3beta inhibitor (AR-A014418) altered the actin cytoskeleton and inhibited migration, mimicking the effects of polyamine depletion. Thus, our results indicate that sustained activation of Akt in response to polyamine depletion inhibits migration through GSK-3beta and Rac1.
肠道上皮细胞（IEC）的快速迁移对黏膜伤口愈合至关重要。我们之前已表明多胺耗竭会抑制IEC-6细胞的迁移。Akt激活及其下游靶点糖原合成酶激酶-3β（GSK-3β）参与了迁移的调控。在此，我们研究了磷脂酰肌醇3-激酶（PI3K）/Akt信号通路增强对多胺耗竭细胞迁移的意义。多胺耗竭的细胞具有较高的Akt（Ser473）和GSK-3β（Ser9）磷酸化水平。用20微摩尔/升LY294002（PI3K抑制剂）预处理30分钟可抑制Akt磷酸化，通过激活多胺耗竭的IEC-6细胞中的Rac1增加迁移，并使肌动蛋白结构恢复至与在对照培养基中生长的细胞相似。用GSK-3β抑制剂（AR-A014418）处理细胞会改变肌动蛋白细胞骨架并抑制迁移，模拟多胺耗竭的作用。因此，我们的结果表明，多胺耗竭导致的Akt持续激活通过GSK-3β和Rac1抑制迁移。
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