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Cell Motil Cytoskeleton. 2009 Jan;66(1):36-47. doi: 10.1002/cm.20323.

WAVE2 is regulated by multiple phosphorylation events within its VCA domain.

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  • 1Department of Biochemistry, Faculty of Medical and Veterinary Sciences, University of Bristol, Bristol, United Kingdom.

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.

(c) 2008 Wiley-Liss, Inc.

PMID:
19012317
[PubMed - indexed for MEDLINE]
PMCID:
PMC2798068
Free PMC Article

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