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Sci. Signal., 8 September 2009
Vol. 2, Issue 87, p. ra52
[DOI: 10.1126/scisignal.2000393]


The Tyrosine Kinase Fer Is a Downstream Target of the PLD-PA Pathway that Regulates Cell Migration

Toshiki Itoh1*, Junya Hasegawa1, Kazuya Tsujita2, Yasunori Kanaho3, and Tadaomi Takenawa2*

1 Division of Membrane Biology, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
2 Division of Lipid Biochemistry, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
3 Department of Physiological Chemistry, Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba 305-0006, Japan.

Abstract: Phosphatidic acid (PA), which can be produced by phospholipase D (PLD), is involved in various signaling events, such as cell proliferation, survival, and migration. However, the molecular mechanisms that link PA to cell migration are largely unknown. Here, we show that PA binds to the tyrosine kinase Fer and enhances its ability to phosphorylate cortactin, a protein that promotes actin polymerization. We found that a previously unknown lipid-binding module in Fer adjacent to the F-BAR [Fes-Cdc42–interacting protein 4 (CIP4) homology (FCH) and bin-amphiphysin-Rvs] domain mediated PA binding. We refer to this lipid-binding domain as the FX (F-BAR extension) domain. Overexpression of Fer enhanced lamellipodia formation and cell migration in a manner dependent on PLD activity and the PA-FX interaction. Thus, the PLD-PA pathway promotes cell migration through Fer-induced enhancement of actin polymerization.

* To whom correspondence should be addressed. E-mail: takenawa{at} (T.T.) and titoh{at} (T.I.)

Citation: T. Itoh, J. Hasegawa, K. Tsujita, Y. Kanaho, T. Takenawa, The Tyrosine Kinase Fer Is a Downstream Target of the PLD-PA Pathway that Regulates Cell Migration. Sci. Signal. 2, ra52 (2009).

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