Effect of WAVE2 Phosphorylation on Activation of the Arp2/3 Complex
Abstract
Members of the family of WASP-family Verprolin homologous proteins (WAVEs) activate the Arp2/3 complex to induce actin polymerization. The WAVE family comprises three proteins, namely, WAVE1, WAVE2 and WAVE3. Among them, WAVE2 is crucial for activation of the Arp2/3 complex for the formation of branched actin filaments in lamellipodia. Activation of mitogen-activated protein (MAP) kinase signalling results in the phosphorylation of the WAVE family proteins; however, which of the three WAVE proteins is phosphorylated is unclear. We found that in vitro WAVE2 is directly phosphorylated by a MAP kinase, i.e. extracellular signal-regulated kinase (ERK) 2. The proline-rich region and the verprolin, cofilin and acidic (VCA) region of WAVE2 were phosphorylated. Interestingly, the phosphorylated VCA region had a higher affinity for the Arp2/3 complex. However, the phosphorylation of the VCA region resulted in reduced induction of Arp2/3-mediated actin polymerization in vitro. The role of the phosphorylation of the proline-rich region was not determined.
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WAVE2 is phosphorylated by ERK or JNK at Ser308, Ser343, Thr346 and Ser351, and this phosphorylation is necessary for actin polymerization and the migration of cultured cell lines.
“WAVE2 is phosphorylated by extracellular signal-regulated kinase (ERK) or Jun N-terminal kinase (JNK) at Ser308, Ser343, Thr346 and Ser351, and this phosphorylation is necessary for actin polymerization and the migration of cultured cell lines41–43.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [43]
CK2 phosphorylation of the WCA domain of WAVEs and/or CDK5 phosphorylation of the proline-rich region of WAVE1 may confer an inhibitory state, whereas protein phosphatase-mediated dephosphorylation of these sites may activate the WAVE complex.
“Thus, CK2 phosphorylation of the WCA domain of WAVEs and/or CDK5 phosphorylation of the proline-rich region of WAVE1 may confer an inhibitory state, whereas protein phosphatase-mediated dephosphorylation of these sites may activate the WAVE complex22,43,44,48,49.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [43]
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Takenawa, T., & Miki, H. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.10.1801 · Cited by 604 · see citing works
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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
- Nakanishi, O., Suetsugu, S., Yamazaki, D., & Takenawa, T.
- Affiliations
- Japan Science and Technology Agency (JP)
- Corresponding author
- Takenawa, T.
- Venue
- Journal of Biochemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-12-19
- Volume
- 141
- Issue
- 3
- Pages
- 319-325
- ISSN
- 0021-924X (ISSN-L)
- OpenAlex
- W1978082911
- Cited by
- 50
- References
- 1
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 2 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 4 · 2012: 1
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- 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 › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- WAVE2, Arp2/3 complex, MAPK signaling, ERK2 phosphorylation, proline-rich region, actin polymerization, branched actin filaments, lamellipodia, protein phosphorylation
- MeSH terms
- Actins, Amino Acid Sequence, Animals, Butadienes, Cells, Cultured, Fibroblasts, Nitriles, Phosphorylation, Pseudopodia, Amino Acid Substitution, Mitogen-Activated Protein Kinase 1, Wiskott-Aldrich Syndrome Protein Family, Actin-Related Protein 2-3 Complex, Mice
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