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Cited by 66Cellular Mechanics and InteractionsProtein Kinase Regulation and GTPase SignalingAxon Guidance and Neuronal Signaling

Phosphorylation of WAVE2 by MAP kinases regulates persistent cell migration and polarity

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Danson, Christopher M., Pocha, Shirin M., Bloomberg, Graham B., Cory, Giles O.·2007·Journal of Cell Science
DOI 10.1242/jcs.013714PMC PMC2690415
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Abstract

The WAVE family of proteins has long been implicated in the stimulus-dependent generation of lamellipodia at the leading edge of migrating cells, with WAVE2 in particular implicated in the formation of peripheral ruffles and chemotactic migration. However, the lack of direct visualisation of cell migration in WAVE2 mutants or knockdowns has made defining the mechanisms of WAVE2 regulation during cell migration difficult. We have characterised three MAP kinase phosphorylation sites within WAVE2 and analysed fibroblast behaviour in a scratch-wound model following introduction of transgenes encoding phospho-defective WAVE2. The cells exhibited an increase in migration speed, a decrease in the persistence of migration, and disruption of polarisation of the Golgi apparatus. All these effects could be mimicked by acute knockdown of endogenous WAVE2 expression with RNAi, indicating that phosphorylation of WAVE2 by MAP kinases regulates cell polarity during migration.

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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 [42]

    The Results (‘Phosphorylation of WAVE2 in vivo’) identify ERK/JNK phosphorylation at Ser343, Thr346 and Ser351, but not Ser308. The Results (‘The function of WAVE2 phosphorylation’) found no difference in in-vitro actin-polymerisation activity between wild-type and phospho-defective WAVE2. The migration Results show that phosphorylation regulates directional persistence in cultured fibroblasts, not that it is necessary for migration: phospho-defective cells still migrated, and moved faster. (LLM, conf=0.90)

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Research works printed but not linked: 37

  1. Ardern H Sandilands E Machesky LM Timpson P Frame MC Brunton VG Src-dependent phosphorylation of Scar1 promotes its association with the Arp2/3 complex Cell Motil. Cytoskeleton 2006 63 6 13 16317717
  2. Bershadsky AD Futerman AH Disruption of the Golgi apparatus by brefeldin A blocks cell polarization and inhibits directed cell migration Proc. Natl. Acad. Sci. USA 1994 91 5686 5689 8202549 PMC44061
  3. Bompard G Caron E Regulation of WASP/WAVE proteins: making a long story short J. Cell Biol 2004 166 957 962 15452139 PMC2172026
  4. Cory GO Cramer R Blanchoin L Ridley AJ Phosphorylation of the WASP-VCA domain increases its affinity for the Arp2/3 complex and enhances actin polymerization by WASP Mol. Cell 2003 11 1229 1239 12769847
  5. Dawson JC Legg JA Machesky LM Bar domain proteins: a role in tubulation, scission and actin assembly in clathrin-mediated endocytosis Trends Cell Biol 2006 16 493 498 16949824
  6. Demaison C Parsley K Brouns G Scherr M Battmer K Kinnon C Grez M Thrasher AJ High-level transduction and gene expression in hematopoietic repopulating cells using a human immunodeficiency [correction of imunodeficiency] virus type 1-based lentiviral vector containing an internal spleen focus forming virus promoter Hum. Gene Ther 2002 13 803 813 11975847
  7. Dormann D Weijer CJ Chemotactic cell movement during development Curr. Opin. Genet. Dev 2003 13 358 364 12888008
  8. Eden S Rohatgi R Podtelejnikov AV Mann M Kirschner MW Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck Nature 2002 418 790 793 12181570
  9. Gautreau A Ho HY Li J Steen H Gygi SP Kirschner MW Purification and architecture of the ubiquitous Wave complex Proc. Natl. Acad. Sci. USA 2004 101 4379 4383 15070726 PMC384755
  10. Gomes ER Jani S Gundersen GG Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells Cell 2005 121 451 463 15882626
  11. Gundersen GG Gomes ER Wen Y Cortical control of microtubule stability and polarization Curr. Opin. Cell Biol 2004 16 106 112 15037313
  12. Gupton SL Anderson KL Kole TP Fischer RS Ponti A Hitchcock-DeGregori SE Danuser G Fowler VM Wirtz D Hanein D Cell migration without a lamellipodium: translation of actin dynamics into cell movement mediated by tropomyosin J. Cell Biol 2005 168 619 631 15716379 PMC2171771
  13. Hahne P Sechi A Benesch S Small JV Scar/WAVE is localised at the tips of protruding lamellipodia in living cells FEBS Lett 2001 49 215 220 11257497
  14. Ibarra N Pollitt A Insall RH Regulation of actin assembly by SCAR/WAVE proteins Biochem. Soc. Trans 2005 33 1243 1246 16246088
  15. Innocenti M Zucconi A Disanza A Frittoli E Areces LB Steffen A Stradal TE Di Fiore PP Carlier MF Scita G Abi1 is essential for the formation and activation of a WAVE2 signalling complex Nat. Cell Biol 2004 6 319 327 15048123
  16. Johnson GL Lapadat R Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases Science 2002 298 1911 1912 12471242
  17. Kawamura K Takano K Suetsugu S Kurisu S Yamazaki D Miki H Takenawa T Endo T N-WASP and WAVE2 acting downstream of phosphatidylinositol 3-kinase are required for myogenic cell migration induced by hepatocyte growth factor J. Biol. Chem 2004 279 54862 54871 15496413
  18. Kheir WA Gevrey JC Yamaguchi H Isaac B Cox D A WAVE2-Abi1 complex mediates CSF-1-induced F-actin-rich membrane protrusions and migration in macrophages J. Cell Sci 2005 118 5369 5379 16280551
  19. Kurisu S Suetsugu S Yamazaki D Yamaguchi H Takenawa T Rac-WAVE2 signaling is involved in the invasive and metastatic phenotypes of murine melanoma cells Oncogene 2005 24 1309 1319 15608687
  20. Leng Y Zhang J Badour K Arpaia E Freeman S Cheung P Siu M Siminovitch K Abelson-interactor-1 promotes WAVE2 membrane translocation and Abelson-mediated tyrosine phosphorylation required for WAVE2 activation Proc. Natl. Acad. Sci. USA 2005 102 1098 1103 15657136 PMC545868
  21. Magdalena J Millard TH Etienne-Manneville S Launay S Warwick HK Machesky LM Involvement of the Arp2/3 complex and Scar2 in Golgi polarity in scratch wound models Mol. Biol. Cell 2003a 14 670 684 12589062 PMC150000
  22. Magdalena J Millard TH Machesky LM Microtubule involvement in NIH 3T3 Golgi and MTOC polarity establishment J. Cell Sci 2003b 116 743 756 12538774
  23. Miki H Suetsugu S Takenawa T WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac EMBO J 1998 17 6932 6941 9843499 PMC1171041
  24. Miki H Fukuda M Nishida E Takenawa T Phosphorylation of WAVE downstream of mitogen-activated protein kinase signaling J. Biol. Chem 1999 274 27605 27609 10488099
  25. Nakanishi O Suetsugu S Yamazaki D Takenawa T Effect of WAVE2 phosphorylation on activation of the Arp2/3 complex J. Biochem 2007 141 319 325 17202194
  26. Nobes CD Hall A Rho GTPases control polarity, protrusion, and adhesion during cell movement J. Cell Biol 1999 144 1235 1244 10087266 PMC2150589
  27. Pollard TD Regulation of actin filament assembly by arp2/3 complex and formins Annu. Rev. Biophys. Biomol. Struct 2007 36 451 477 17477841
  28. Ponti A Machacek M Gupton SL Waterman-Storer CM Danuser G Two distinct actin networks drive the protrusion of migrating cells Science 2004 305 1782 1786 15375270
  29. Prigozhina NL Waterman-Storer CM Protein kinase D-mediated anterograde membrane trafficking is required for fibroblast motility Curr. Biol 2004 14 88 98 14738729
  30. Ridley AJ Schwartz MA Burridge K Firtel RA Ginsberg MH Borisy G Parsons JT Horwitz AR Cell migration: integrating signals from front to back Science 2003 302 1704 1709 14657486
  31. Rodriguez OC Schaefer AW Mandato CA Forscher P Bement WM Waterman-Storer CM Conserved microtubule-actin interactions in cell movement and morphogenesis Nat. Cell Biol 2003 5 599 609 12833063
  32. Stuart JR Gonzalez FH Kawai H Yuan ZM c-Abl interacts with the WAVE2 signaling complex to induce membrane ruffling and cell spreading J. Biol. Chem 2006 281 31290 31297 16899465
  33. Suetsugu S Yamazaki D Kurisu S Takenawa T Differential roles of WAVE1 and WAVE2 in dorsal and peripheral ruffle formation for fibroblast cell migration Dev. Cell 2003 5 595 609 14536061
  34. Suetsugu S Kurisu S Oikawa T Yamazaki D Oda A Takenawa T Optimization of WAVE2 complex-induced actin polymerization by membrane-bound IRSp53, PIP(3), and Rac J. Cell Biol 2006 173 571 585 16702231 PMC2063866
  35. Welch MD Mitchison TJ Purification and assay of the platelet Arp2/3 complex Methods Enzymol 1998 298 52 61 9751871
  36. Yamazaki D Suetsugu S Miki H Kataoka Y Nishikawa S Fujiwara T Yoshida N Takenawa T WAVE2 is required for directed cell migration and cardiovascular development Nature 2003 424 452 456 12879075
  37. Yan C Martinez-Quiles N Eden S Shibata T Takeshima F Shinkura R Fujiwara Y Bronson R Snapper SB Kirschner MW WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility EMBO J 2003 22 3602 3612 12853475 PMC165620

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Authors
Danson, C. M., Pocha, S. M., Bloomberg, G. B., & Cory, G. O.
Affiliations
  • Department of Biochemistry, Faculty of Medical and Veterinary Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK
  • University of Bristol (GB)
ORCID
Pocha, Shirin M.
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2007-12-01
Volume
120
Issue
23
Pages
4144-4154
ISSN
  • 0021-9533 (ISSN-L)
  • 1477-9137
DOI
10.1242/jcs.013714
PMC
PMC2690415
OpenAlex
W1968661759
Cited by
66
References
1
Citations by year
2025: 1 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 5 · 2012: 5
FWCI
1.41
Type
journal article
Language
en
Open access
Locations
  • Journal of Cell Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
Wellcome Trust (071330)
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, MAPK phosphorylation, cell migration, migration persistence, cell polarity, Golgi apparatus, lamellipodia, fibroblasts, chemotaxis, wound healing
MeSH terms
Animals, Cell Movement, Chlorocebus aethiops, Fibroblasts, Phosphorylation, Precipitin Tests, Cell Polarity, Protein Structure, Tertiary, Transgenes, COS Cells, Mitogen-Activated Protein Kinases, RNA Interference, RNA, Small Interfering, NIH 3T3 Cells, Green Fluorescent Proteins, Wiskott-Aldrich Syndrome Protein Family, Mice

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