Involvement of 14-3-3 Proteins in the Second Epidermal Growth Factor-induced Wave of Rac1 Activation in the Process of Cell Migration
Involvement of 14-3-3 Proteins in the Second Epidermal Growth Factor-induced Wave of Rac1 Activation in the Process of Cell Migration
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DOI：
10.1074/jbc.m111.255489
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发表时间：
2011-11-11
影响因子：
4.8
通讯作者：
Imoto, Masaya
中科院分区：
文献类型：
--
作者：
Kobayashi, Hiroki;Ogura, Yusuke;Imoto, Masaya
以往的大量工作已经阐明了Rho家族小GTP酶调控细胞迁移、肌动蛋白重塑的核心机制，包括RhoA、CDC42和rac1；然而，这些分子的时空调控在很大程度上仍然不清楚。在此，我们报道了EGF在细胞迁移过程中诱导了两相的rac1激活，细胞迁移抑制剂UTKO1抑制了EGF诱导的rac1激活的第二波，但不抑制第一波。为了研究第二波rac1激活的调控机制和作用，我们确定14-3-3xi是UTKO1的靶蛋白，并发现UTKO1取消了14-3-3xi与Tiam1的结合，这可能是14-3-3xi与Tiam1相互作用的结果。据我们所知，这是第一个使用化学遗传学方法来证明rac1的时间激活机制的报告。
Immense previous efforts have elucidated the core machinery in cell migration, actin remodeling regulated by Rho family small GTPases including RhoA, Cdc42, and Rac1; however, the spatiotemporal regulation of these molecules remains largely unknown. Here, we report that EGF induces biphasic Rac1 activation in the process of cell migration, and UTKO1, a cell migration inhibitor, inhibits the second EGF-induced wave of Rac1 activation but not the first wave. To address the regulation mechanism and role of the second wave of Rac1 activation, we identified 14-3-3 xi as a target protein of UTKO1 and also showed that UTKO1 abrogated the binding of 14-3-3 xi to Tiam1 that was responsible for the second wave of Rac1 activation, suggesting that the interaction of 14-3-3 xi with Tiam1 is involved in this event. To our knowledge, this is the first report to use a chemical genetic approach to demonstrate the mechanism of temporal activation of Rac1.