Involvement of 14-3-3 proteins in the second epidermal growth factor-induced wave of Rac1 activation in the process of cell migration

Hiroki Kobayashi, Yusuke Ogura, Masato Sawada, Ryoji Nakayama, Kei Takano, Yusuke Minato, Yasushi Takemoto, Etsu Tashiro, Hidenori Watanabe, Masaya Imoto

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31 Citations (Scopus)

Abstract

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 14-3-3ξ as a target protein of UTKO1 and also showed that UTKO1 abrogated the binding of 14-3-3ξ to Tiam1 that was responsible for the second wave of Rac1 activation, suggesting that the interaction of 14-3-3ξ 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.

Original languageEnglish
Pages (from-to)39259-39268
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number45
DOIs
Publication statusPublished - 2011 Nov 11

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Kobayashi, H., Ogura, Y., Sawada, M., Nakayama, R., Takano, K., Minato, Y., Takemoto, Y., Tashiro, E., Watanabe, H., & Imoto, M. (2011). Involvement of 14-3-3 proteins in the second epidermal growth factor-induced wave of Rac1 activation in the process of cell migration. Journal of Biological Chemistry, 286(45), 39259-39268. https://doi.org/10.1074/jbc.M111.255489