title: Involvement of 14-3-3 proteins in the second epidermal growth factor-induced wave of Rac1 activation in the process of cell migration.
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 14-3-3ζ as a target protein of UTKO1 and also showed that UTKO1 abrogated the binding of 14-3-3ζ to Tiam1 that was responsible for the second wave of Rac1 activation, suggesting that the interaction of 14-3-3ζ 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.
authors.affiliation: Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ogura
authors.forename: Masato
authors.initials: M
authors.lastname: Sawada
authors.forename: Ryoji
authors.initials: R
authors.lastname: Nakayama
authors.forename: Kei
authors.initials: K
authors.lastname: Takano
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Minato
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Etsu
authors.initials: E
authors.lastname: Tashiro
authors.forename: Hidenori
authors.initials: H
authors.lastname: Watanabe
authors.forename: Masaya
authors.initials: M
authors.lastname: Imoto
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D001547:Benzaldehydes / Q000494:pharmacology; D002460:Cell Line; D002465:Cell Movement; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; D001547:Benzaldehydes; D020662:Guanine Nucleotide Exchange Factors; C107953:RAC1 protein, human; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; C558668:UTKO1 compound; C482983:YWHAE protein, human; D004815:Epidermal Growth Factor; D020830:rac1 GTP-Binding Protein