WAVE2 is regulated by multiple phosphorylation events within its VCA domain
Open accessAbstract
The (Wiskott‐Aldrich Syndrome Protein)‐family verprolin homologous protein (WAVE) family of proteins occupies a pivotal position in the cell, converting extracellular signals into the formation of branched filamentous (F) actin structures. WAVE proteins contain a verprolin central acidic (VCA) domain at their C‐terminus, responsible for binding to and activating the Arp2/3 complex, which in‐turn nucleates the formation of new actin filaments. Here we identify five Casein Kinase 2 (CK2) phosphorylation sites within the VCA domain of WAVE2, serines 482, 484, 488, 489, and 497. Phosphorylation of these sites is required for a high affinity interaction with the Arp2/3 complex. Phosphorylation of ser 482 and 484 specifically inhibits the activation of the Arp2/3 complex by the WAVE2 VCA domain, but has no effect on the affinity for the Arp2/3 complex when the other phosphorylation sites are occupied. We demonstrate phosphorylation of all five sites on endogenous WAVE2 and show that their mutation to non‐phosphorylatable alanine residues inhibits WAVE2 function in vivo, inhibiting cell ruffling and disrupting the integrity of the leading edge of migrating cells. Cell Motil. Cytoskeleton 2008. © 2008 Wiley‐Liss, Inc.
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CK2 phosphorylates Ser482, 484, 488, 489 and 497 within the acidic region of the WCA domain of WAVE2.
“Casein kinase 2 (CK2) phosphorylates Ser482, 484, 488, 489 and 497 within the acidic region of the WCA domain of WAVE248.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [48]
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Kim, K. S., Marcogliese, P. C., Yang, J., Callaghan, S. M., Resende, V., Abdel-Messih, E., Marras, C., Visanji, N. P., Huang, J., Schlossmacher, M. G., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1718946115 · Cited by 111 · see citing works
Ura, S., Pollitt, A. Y., Veltman, D. M., Morrice, N. A., Machesky, L. M., & Insall, R. H. (2012) · Current Biology · doi:10.1016/j.cub.2012.02.020 · Cited by 50 · see citing works
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
- Pocha, S. M., & Cory, G. O.
- Affiliations
- University of Bristol (GB)
- Corresponding author
- Cory, Giles O.
- ORCID
- Pocha, Shirin M.
- Venue
- Cell Motility
- Publisher
- Wiley
- Published
- 2008-11-14
- Volume
- 66
- Issue
- 1
- Pages
- 36-47
- ISSN
- 0886-1544 (ISSN-L)
- PMC
- PMC2798068
- OpenAlex
- W2093715366
- Cited by
- 55
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 3 · 2015: 2 · 2014: 5 · 2013: 6 · 2012: 3
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Motility and the Cytoskeleton (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open Research Exeter (University of Exeter) (publishedVersion)
- Figshare (submittedVersion)
- Funders
- Wellcome Trust
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- WAVE2, Arp2/3 complex, branched actin filaments, actin nucleation, cell migration, phosphorylation sites
- MeSH terms
- Amino Acid Sequence, Animals, Cell Movement, Chlorocebus aethiops, Humans, Molecular Sequence Data, Phosphorylation, Pseudopodia, Protein Structure, Tertiary, COS Cells, Mitogen-Activated Protein Kinases, NIH 3T3 Cells, Casein Kinase II, Protein Kinase Inhibitors, Wiskott-Aldrich Syndrome Protein Family, Actin-Related Protein 2-3 Complex, Mice, Rats
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