c-Abl-mediated Phosphorylation of WAVE3 Is Required for Lamellipodia Formation and Cell Migration
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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.
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ABL tyrosine kinase phosphorylates Tyr151 of WAVE1, Tyr150 of WAVE2 or Tyr151 of WAVE3, and this phosphorylation is suggested to interfere with the interaction between the WAVE meander region and CYFIP, releasing the WCA region for ARP2/3 activation.
“The ABL tyrosine kinase phosphorylates Tyr151 of WAVE1, Tyr150 of WAVE2 or Tyr151 of WAVE337,38, and this phosphorylation is suggested to interfere with the interaction between the WAVE meander region and CYFIP, releasing the WCA region for ARP2/3 activation21 (Figs. 2 and 3a–c).”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [37]
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Kunda, P., Craig, G., Dominguez, V., & Baum, B. (2003) · Current Biology · doi:10.1016/j.cub.2003.10.005 · Cited by 341 · see citing works
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- Leng, Y., Zhang, J., Badour, K., Arpaia, E., Freeman, S., Cheung, P., Siu, M., and Siminovitch, K. (2005) Proc. Natl. Acad. Sci. U. S. A. 102, 1098 -1103
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The WAVE complex in developmental and adulthood brain disorders
Kim, H.-G., Berdasco, C., Nairn, A. C., & Kim, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01386-w · Cited by 8 · see citing works
- Authors
- Sossey-Alaoui, K., Li, X., & Cowell, J. K.
- Affiliations
- Roswell Park Comprehensive Cancer Center (US)
- ORCID
- Cowell, John K.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-09
- Volume
- 282
- Issue
- 36
- Pages
- 26257-26265
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2121034339
- Cited by
- 93
- References
- 1
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 3 · 2015: 6 · 2014: 10 · 2013: 6 · 2012: 6
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- American Cancer Society (CA16056)
- National Institutes of Health (CA16056)
- Novartis Pharma
- National Cancer Institute (CA 16056., P30CA016056)
- National Institute of Neurological Disorders and Stroke (R01NS035791, NS 35791)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- WAVE3, c-Abl, tyrosine phosphorylation, lamellipodia formation, cell migration, Arp2/3 complex, actin cytoskeleton remodeling, platelet-derived growth factor, imatinib, non-receptor tyrosine kinase
- MeSH terms
- Imatinib Mesylate, Actins, Benzamides, Cell Movement, Cytoskeleton, Humans, Piperazines, Protein Processing, Post-Translational, Pseudopodia, Pyrimidines, Proto-Oncogene Proteins c-abl, rac GTP-Binding Proteins, Cell Line, Tumor, Protein Kinase Inhibitors, Wiskott-Aldrich Syndrome Protein Family, Actin-Related Protein 2-3 Complex
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