title: Upon Wnt stimulation, Rac1 activation requires Rac1 and Vav2 binding to p120-catenin.
abstract: A role for Rac1 GTPase in canonical Wnt signaling has recently been demonstrated, showing that it is required for β-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.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, CEB, Facultat de Medicina, Universitat Autònoma de Barcelona, E-08193 Bellaterra,  Spain.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Valls
authors.forename: Montserrat
authors.initials: M
authors.lastname: Codina
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Miller
authors.forename: Beatriz
authors.initials: B
authors.lastname: Del Valle-Pérez
authors.forename: Meritxell
authors.initials: M
authors.lastname: Vinyoles
authors.forename: Carme
authors.initials: C
authors.lastname: Caelles
authors.forename: Pierre D
authors.initials: PD
authors.lastname: McCrea
authors.forename: Antonio
authors.initials: A
authors.lastname: García de Herreros
authors.forename: Mireia
authors.initials: M
authors.lastname: Duñach
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D051177:Catenins / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D054262:Gastrulation / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D050505:Mutant Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D060509:Wnt3A Protein / Q000494:pharmacology*; D014981:Xenopus / Q000196:embryology / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D050505:Mutant Proteins; D051567:Proto-Oncogene Proteins c-vav; C093651:VAV2 protein, human; D060509:Wnt3A Protein; D051176:beta Catenin; D010768:Phosphoserine; D019000:Phosphotyrosine; D020830:rac1 GTP-Binding Protein; D000095002:Delta Catenin