Effect of WAVE2 phosphorylation on activation of the Arp2/3 complex

J Biochem. 2007 Mar;141(3):319-25. doi: 10.1093/jb/mvm034. Epub 2007 Jan 3.

Abstract

Members of the family of WASP-family Verprolin homologous proteins (WAVEs) activate the Arp2/3 complex to induce actin polymerization. The WAVE family comprises three proteins, namely, WAVE1, WAVE2 and WAVE3. Among them, WAVE2 is crucial for activation of the Arp2/3 complex for the formation of branched actin filaments in lamellipodia. Activation of mitogen-activated protein (MAP) kinase signalling results in the phosphorylation of the WAVE family proteins; however, which of the three WAVE proteins is phosphorylated is unclear. We found that in vitro WAVE2 is directly phosphorylated by a MAP kinase, i.e. extracellular signal-regulated kinase (ERK) 2. The proline-rich region and the verprolin, cofilin and acidic (VCA) region of WAVE2 were phosphorylated. Interestingly, the phosphorylated VCA region had a higher affinity for the Arp2/3 complex. However, the phosphorylation of the VCA region resulted in reduced induction of Arp2/3-mediated actin polymerization in vitro. The role of the phosphorylation of the proline-rich region was not determined.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / metabolism*
  • Actins / metabolism
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Butadienes / pharmacology
  • Cells, Cultured
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Nitriles / pharmacology
  • Phosphorylation
  • Pseudopodia / physiology
  • Wiskott-Aldrich Syndrome Protein Family / metabolism*

Substances

  • Actin-Related Protein 2-3 Complex
  • Actins
  • Butadienes
  • Nitriles
  • U 0126
  • Wasf2 protein, mouse
  • Wiskott-Aldrich Syndrome Protein Family
  • Mitogen-Activated Protein Kinase 1