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Originally published In Press as doi:10.1074/jbc.M604323200 on August 18, 2006
J. Biol. Chem., Vol. 281, Issue 42, 31972-31986, October 20, 2006
Interaction of Phospholipase C- 1 with Villin Regulates Epithelial Cell Migration*
Alok Tomar,
Sudeep George,
Pallavi Kansal,
Yaohong Wang, and
Seema Khurana1
From the
Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163
Tyrosine-phosphorylated villin regulates actin dynamics, cell morphology, and cell migration. Previously, we identified four tyrosine phosphorylation sites in the amino-terminal domain of villin. In this study we report six new sites in the carboxyl-terminal region of the villin core. With this study we document all phosphorylatable tyrosine residues in villin and map them to functions of villin. In this study, we identify for the first time the functional relevance of the carboxyl-terminal domains of the villin core. Expression of the carboxyl-terminal phosphorylation site mutant, as well as the villin truncation mutant S1-S3, inhibited cell migration in HeLa and Madin-Darby canine kidney Tet-Off cells, confirming the role of the carboxyl-terminal phosphorylation sites in villin-induced cell migration. The carboxyl-terminal phosphorylation sites were found to be critical for the interaction of villin with its ligand phospholipase C- 1 and for its localization to the developing lamellipodia in a motile cell. The results presented here elucidate the molecular basis for tyrosine-phosphorylated villin-induced changes in cell motility.
Received for publication, May 5, 2006
, and in revised form, July 31, 2006.
* This work was supported by NIDDK Grants DK-65006 and DK-54755 from the National Institutes of Health (to S. K.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. 1-4 and Videos 1-5.
1 To whom correspondence should be addressed: Dept. of Physiology, the University of Tennessee Health Science Center, Nash 402, 894 Union Ave., Memphis, TN 38163. Tel.: 901-448-3410; Fax: 901-448-3505; E-mail: skhurana{at}utmem.edu.

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Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.
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