c-Abl-mediated Phosphorylation of WAVE3 Is Required for Lamellipodia Formation and Cell Migration

• Published in: The Journal of biological chemistry Vol. 282; no. 36; pp. 26257 - 26265
• Main Authors: Sossey-Alaoui, Khalid, Li, Xiurong, Cowell, John K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.09.2007; American Society for Biochemistry and Molecular Biology
• Subjects: Actin-Related Protein 2-3 Complex - metabolism; Actins - metabolism; Benzamides; Cell Line, Tumor; Cell Movement - drug effects; Cell Movement - physiology; Cytoskeleton - metabolism; Humans; Imatinib Mesylate; Piperazines - pharmacology; Protein Kinase Inhibitors - pharmacology; Protein Processing, Post-Translational - drug effects; Protein Processing, Post-Translational - physiology; Proto-Oncogene Proteins c-abl - antagonists & inhibitors; Proto-Oncogene Proteins c-abl - metabolism; Pseudopodia - metabolism; Pyrimidines - pharmacology; rac GTP-Binding Proteins - metabolism; Wiskott-Aldrich Syndrome Protein Family - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M701484200

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.