c-Abl-mediated phosphorylation of WAVE3 is required for lamellipodia formation and cell migration.
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.
Sossey-Alaoui
Khalid
K
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. khalid.sossey-alaoui@roswellpark.org
Li
Xiurong
X
Cowell
John K
JK
D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D001549:Benzamides; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology*; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C120153:WASF3 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; D000068877:Imatinib Mesylate; D016315:Proto-Oncogene Proteins c-abl; D020744:rac GTP-Binding Proteins