TY - JOUR
T1 - Involvement of 14-3-3 proteins in the second epidermal growth factor-induced wave of Rac1 activation in the process of cell migration
AU - Kobayashi, Hiroki
AU - Ogura, Yusuke
AU - Sawada, Masato
AU - Nakayama, Ryoji
AU - Takano, Kei
AU - Minato, Yusuke
AU - Takemoto, Yasushi
AU - Tashiro, Etsu
AU - Watanabe, Hidenori
AU - Imoto, Masaya
PY - 2011/11/11
Y1 - 2011/11/11
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M111.255489
DO - 10.1074/jbc.M111.255489
M3 - Article
C2 - 21868386
AN - SCOPUS:80655144755
VL - 286
SP - 39259
EP - 39268
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 45
ER -