Phosphorylation of the WASP-VCA domain increases its affinity for the Arp2/3 complex and enhances actin polymerization by WASP

Mol Cell. 2003 May;11(5):1229-39. doi: 10.1016/s1097-2765(03)00172-2.

Abstract

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.

MeSH terms

  • 3T3 Cells
  • Actin-Related Protein 2
  • Actin-Related Protein 3
  • Actins / biosynthesis*
  • Amino Acid Sequence / genetics
  • Animals
  • Antibody Specificity / immunology
  • Binding Sites / genetics
  • COS Cells
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Eukaryotic Cells / metabolism*
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Phosphorylation
  • Polymers / metabolism
  • Protein Structure, Tertiary / genetics
  • Proteins / genetics
  • Proteins / metabolism*
  • Serine / metabolism
  • Up-Regulation / genetics*
  • Wiskott-Aldrich Syndrome Protein
  • Wiskott-Aldrich Syndrome Protein, Neuronal

Substances

  • Actin-Related Protein 2
  • Actin-Related Protein 3
  • Actins
  • Actr2 protein, mouse
  • Actr3 protein, mouse
  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • Polymers
  • Proteins
  • Was protein, mouse
  • Wasl protein, mouse
  • Wiskott-Aldrich Syndrome Protein
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • Serine