c-Abl-mediated phosphorylation of WAVE3 is required for lamellipodia formation and cell migration

Khalid Sossey-Alaoui, Xiurong Li, John Kenneth Cowell

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)26257-26265
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number36
DOIs
StatePublished - Sep 7 2007
Externally publishedYes

Fingerprint

Phosphorylation
Pseudopodia
Cell Movement
Tyrosine
Actins
Wiskott-Aldrich Syndrome Protein Family
Wiskott-Aldrich Syndrome
GTP Phosphohydrolases
Platelet-Derived Growth Factor
Cytoskeleton
Actin Cytoskeleton
Protein-Tyrosine Kinases
Cultured Cells
Phosphotransferases
Chemical activation
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

c-Abl-mediated phosphorylation of WAVE3 is required for lamellipodia formation and cell migration. / Sossey-Alaoui, Khalid; Li, Xiurong; Cowell, John Kenneth.

In: Journal of Biological Chemistry, Vol. 282, No. 36, 07.09.2007, p. 26257-26265.

Research output: Contribution to journalArticle

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