dc.contributor.author | Pocha, SM | |
dc.contributor.author | Cory, GO | |
dc.date.accessioned | 2013-11-14T14:12:22Z | |
dc.date.issued | 2009-01 | |
dc.description.abstract | 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. | en_GB |
dc.identifier.citation | Cell Motility and the Cytoskeleton, 2009, Vol. 66, Issue 1, pp. 36 - 47 | en_GB |
dc.identifier.doi | 10.1002/cm.20323 | |
dc.identifier.uri | http://hdl.handle.net/10871/13949 | |
dc.language.iso | en | en_GB |
dc.publisher | Wiley-Blackwell | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/19012317 | en_GB |
dc.relation.url | http://onlinelibrary.wiley.com/doi/10.1002/cm.20323/abstract | en_GB |
dc.subject | Actin-Related Protein 2-3 Complex | en_GB |
dc.subject | Amino Acid Sequence | en_GB |
dc.subject | Animals | en_GB |
dc.subject | COS Cells | en_GB |
dc.subject | Casein Kinase II | en_GB |
dc.subject | Cell Movement | en_GB |
dc.subject | Cercopithecus aethiops | en_GB |
dc.subject | Humans | en_GB |
dc.subject | Mice | en_GB |
dc.subject | Mitogen-Activated Protein Kinases | en_GB |
dc.subject | Molecular Sequence Data | en_GB |
dc.subject | NIH 3T3 Cells | en_GB |
dc.subject | Phosphorylation | en_GB |
dc.subject | Protein Kinase Inhibitors | en_GB |
dc.subject | Protein Structure, Tertiary | en_GB |
dc.subject | Pseudopodia | en_GB |
dc.subject | Rats | en_GB |
dc.subject | Wiskott-Aldrich Syndrome Protein Family | en_GB |
dc.title | WAVE2 is regulated by multiple phosphorylation events within its VCA domain. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2013-11-14T14:12:22Z | |
dc.identifier.issn | 0886-1544 | |
exeter.place-of-publication | United States | |
dc.description | addresses: Department of Biochemistry, Faculty of Medical and Veterinary Sciences, University of Bristol, Bristol, United Kingdom. | en_GB |
dc.description | notes: PMCID: PMC2798068 | en_GB |
dc.description | OnlineOpen Article. This is a copy of an article published in Cell Motility and the Cytoskeleton. This journal is available online at: http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1949-3592 | en_GB |
dc.description | The definitive version is available at www3.interscience.wiley.com | en_GB |
dc.identifier.journal | Cell Motility and the Cytoskeleton | en_GB |