Effect of WAVE2 phosphorylation on activation of the Arp2/3 complex.
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.
Nakanishi
Osamu
O
Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Tokyo 108-8639, Japan.
Suetsugu
Shiro
S
Yamazaki
Daisuke
D
Takenawa
Tadaomi
T
D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011554:Pseudopodia / Q000502:physiology; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000378:metabolism*
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D002070:Butadienes; D009570:Nitriles; C113580:U 0126; C492303:Wasf2 protein, mouse; D051300:Wiskott-Aldrich Syndrome Protein Family; D019950:Mitogen-Activated Protein Kinase 1