Phosphorylation of the WASP-VCA domain increases its affinity for the Arp2/3 complex and enhances actin polymerization by WASP.
Wiskott-Aldrich syndrome protein (WASP) and neural (N)-WASP regulate dynamic actin structures through the ability of their VCA domains to bind to and stimulate the actin nucleating activity of the Arp2/3 complex. Here we identify two phosphorylation sites in the VCA domain of WASP at serines 483 and 484. S483 and S484 are substrates for casein kinase 2 in vitro and in vivo. Phosphorylation of these residues increases the affinity of the VCA domain for the Arp2/3 complex 7-fold and is required for efficient in vitro actin polymerization by the full-length WASP molecule. We propose that constitutive VCA domain phosphorylation is required for optimal stimulation of the Arp2/3 complex by WASP.
Cory
Giles O C
GO
Ludwig Institute for Cancer Research, Royal Free and University College Medical School Branch, Courtauld Building, 91 Riding House Street, London W1W 7BS, United Kingdom.
Cramer
Rainer
R
Blanchoin
Laurent
L
Ridley
Anne J
AJ
D016475:3T3 Cells; D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins / Q000096:biosynthesis*; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D001665:Binding Sites / Q000235:genetics; D019556:COS Cells; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011108:Polymers / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*; D051316:Wiskott-Aldrich Syndrome Protein; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal
D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000199:Actins; C495927:Actr2 protein, mouse; C495929:Actr3 protein, mouse; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D011108:Polymers; D011506:Proteins; C495768:Was protein, mouse; C495772:Wasl protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D012694:Serine