期刊
JOURNAL OF CELL SCIENCE
卷 125, 期 22, 页码 5288-5301出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.101030
关键词
Wnt signaling; p120-catenin; Rac1; Vav2
类别
资金
- Ministerio de Ciencia e Innovacion (MICINN) [BFU2009-07578, SAF2010-16089]
- Asociacion Espanola contra el Cancer (AECC)
- La Fundacio La Marato de TV3 [081731]
- Instituto Carlos III [RD06/0020/0040]
- Generalitat de Catalunya [2009SGR-121, 2009SGR-585]
- MICINN
- National Institutes of Health (NIH) [RO1 M52112]
- March of Dimes [1-FY-07-461-01]
- NIH [HD07325, DK082145]
A role for Rac1 GTPase in canonical Wnt signaling has recently been demonstrated, showing that it is required for beta-catenin translocation to the nucleus. In this study, we investigated the mechanism of Rac1 stimulation by Wnt. Upregulation of Rac1 activity by Wnt3a temporally correlated with enhanced p120-catenin binding to Rac1 and Vav2. Vav2 and Rac1 association with p120-catenin was modulated by phosphorylation of this protein, which was stimulated upon serine/threonine phosphorylation by CK1 and inhibited by tyrosine phosphorylation by Src or Fyn. Acting on these two post-translational modifications, Wnt3a induced the release of p120-catenin from E-cadherin, enabled the interaction of p120-catenin with Vav2 and Rac1, and facilitated Rac1 activation by Vav2. Given that p120-catenin depletion disrupts gastrulation in Xenopus, we analyzed p120-catenin mutants for their ability to rescue this phenotype. In contrast to the wild-type protein or other controls, p120-catenin point mutants that were deficient in the release from E-cadherin or in Vav2 or Rac1 binding failed to rescue p120-catenin depletion. Collectively, these results indicate that binding of p120-catenin to Vav2 and Rac1 is required for the activation of this GTPase upon Wnt signaling.
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