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Originally published In Press as doi:10.1074/jbc.M701484200 on July 9, 2007
J. Biol. Chem., Vol. 282, Issue 36, 26257-26265, September 7, 2007
c-Abl-mediated Phosphorylation of WAVE3 Is Required for Lamellipodia Formation and Cell Migration*
Khalid Sossey-Alaoui1,
Xiurong Li, and
John K. Cowell
From the
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263
The activity of the Wiskott-Aldrich syndrome-related WAVE3 protein is critical for the regulation of the Arp2/3-dependent cytoskeleton organization downstream of Rac-GTPase. The Ableson (Abl) non-receptor tyrosine kinase is also involved in the remolding of actin cytoskeleton in response to extracellular stimuli. Here we show that platelet-derived growth factor stimulation of cultured cells results in WAVE3-Abl interaction and localization to the cell periphery. WAVE3-Abl interaction promotes the tyrosine phosphorylation of WAVE3 by Abl, and STI-571, a specific inhibitor of Abl kinase activity, abrogates the Abl-mediated phosphorylation of WAVE3. We have also shown that Abl targets and phosphorylates four tyrosine residues in WAVE3 and that the Abl-dependent phosphorylation of WAVE3 is critical for the stimulation of lamellipodia formation and cell migration. Our results show that the activation of WAVE3 to promote actin remodeling is enhanced by the c-Abl-mediated tyrosine phosphorylation of WAVE3.
Received for publication, February 20, 2007
, and in revised form, June 6, 2007.
* This work was supported by grants from the National Institutes of Health NS35791 (to J. K. C.), by an Institutional Research Grant IRG02-197 from the American Cancer Society (to K. S. A.), and by the NCI-funded Cancer Center Support, Grant CA16056. 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 information to Fig. 5 (Fig. S5).
1 To whom correspondence should be addressed: Dept. of Cancer Genetics, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263. Tel.: 716-845-1584; Fax: 716-845-3940; E-mail: khalid.sossey-alaoui{at}roswellpark.org.

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Copyright © 2007 by the American Society for Biochemistry and Molecular Biology.
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