Resumen de P120-catenin and rac1: Key players in canonical wnt signaling
A recent role for Rac1 GTPase in canonical Wnt signaling was recently demonstrated, being required for ß-catenin translocation to the nucleus. We find that Rac1 is stimulated in SW-480 or HEK-293 cells upon Wnt3a addition. This up-regulation temporally correlates with p120-catenin direct binding to Rac1 and Vav2, an association that happens after the release of p120-catenin from E-cadherin. p120-catenin and Vav2 are required for Rac1 stimulation by Wnt3a, and for ß-catenin translocation to the nucleus. The interaction of Rac1 and Vav2 with p120-catenin increases upon serine/threonine phosphorylation by CK1 and tyrosine dephosphorylation of p120-catenin, two modifications stimulated by Wnt3a. When over-expressed, p120-catenin mutants unable to bind Rac1 or Vav2 fail to stimulate Rac1 activity. Moreover, since 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 unable to bind Rac1 or Vav2, failed to rescue p120 depletion. Collectively, these results indicate that p120-catenin is required for Rac1 activation upon Wnt signaling, through binding to Vav2 and Rac1 proteins.
