PI3K induced actin filament remodeling through Akt and p70S6K1: implication of essential role in cell migration
PI3K induced actin filament remodeling through Akt and p70S6K1: implication of essential role in cell migration
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DOI：
10.1152/ajpcell.00142.2003
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发表时间：
2004-01-01
影响因子：
5.5
通讯作者：
Jiang, BH
中科院分区：
文献类型：
--
作者：
Qian, Y;Corum, L;Jiang, BH
本研究旨在确定磷脂酰肌醇3-激酶（PI 3 K）诱导的肌动蛋白丝重塑和细胞迁移的分子机制。PI 3 K的活性形式v-P3 k或Myr-P3 k的表达足以诱导肌动蛋白丝重塑，从而导致细胞迁移的增加，以及鸡胚成纤维细胞（CEF）中Akt的激活。使用PI 3 K特异性抑制剂LY-294002抑制PI 3 K活性或破坏Akt活性恢复CEF细胞中肌动蛋白丝的完整性并抑制PI 3 K诱导的细胞迁移。我们还发现，Akt的活化形式（Myr-Akt）的表达足以重塑肌动蛋白丝，从而导致细胞迁移的增加，这不能被LY-294002的存在抑制。此外，我们发现p70 S6 K1激酶是一个下游分子，可以介导PI 3 K和Akt对肌动蛋白丝和细胞迁移的影响。p70 S6 K1的活性形式的过表达足以诱导CEF细胞中的肌动蛋白丝重塑和细胞迁移，这需要Rac活性。这些结果表明，单独激活PI 3 K活性足以重塑肌动蛋白丝，以通过激活CEF细胞中的Akt和p70 S6 K1来增加细胞迁移。
This study was designed to identify the molecular mechanisms of phosphatidylinositol 3-kinase (PI3K)-induced actin filament remodeling and cell migration. Expression of active forms of PI3K, v-P3k or Myr-P3k, was sufficient to induce actin filament remodeling to lead to an increase in cell migration, as well as the activation of Akt in chicken embryo fibroblast (CEF) cells. Either the inhibition of PI3K activity using a PI3K-specific inhibitor, LY-294002, or the disruption of Akt activity restored the integrity of actin filaments in CEF cells and inhibited PI3K-induced cell migration. We also found that expression of an activated form of Akt (Myr-Akt) was sufficient to remodel actin filaments to lead to an increase in cell migration, which was unable to be inhibited by the presence of LY-294002. Furthermore, we found that p70S6K1 kinase was a downstream molecule that can mediate the effects of both PI3K and Akt on actin filaments and cell migration. Overexpression of an active form of p70S6K1 was sufficient to induce actin filament remodeling and cell migration in CEF cells, which requires Rac activity. These results demonstrate that activation of PI3K activity alone is sufficient to remodel actin filaments to increase cell migration through the activation of Akt and p70S6K1 in CEF cells.