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XB-ART-45878
J Cell Sci November 15, 2012; 125 (Pt 22): 5288-301.

Upon Wnt stimulation, Rac1 activation requires Rac1 and Vav2 binding to p120-catenin.

Valls G , Codina M , Miller RK , Del Valle-Pérez B , Vinyoles M , Caelles C , McCrea PD , García de Herreros A , Duñach M .


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.

PubMed ID: 22946057
PMC ID: PMC3561852
Article link: J Cell Sci
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: akt1 cdh1 csnk1a1 ctnnb1 ctnnd1 dvl2 fyn gapdh gstk1 krt8.1 lmnb1 mapk9 myc pak1 pklr rac1 tbx2 vav2 wnt3a zbtb33
Antibodies: Cdh1 Ab4 Cdh2 Ab2 Ctnnd1 Ab1 Ctnnd1 Ab2 Fyn Ab1 Gapdh Ab1 Gstk1 Ab1 Lmnb1 Ab3 Mapk9 Ab1 Mapk9 Ab2 Myc Ab3 Rac1 Ab1 Vav2 Ab1
Morpholinos: ctnnd1 MO1 ctnnd1 MO2


Article Images: [+] show captions
References [+] :
Bustelo, Vav proteins, adaptors and cell signaling. 2001, Pubmed