Regulator of G-protein signaling 3 isoform 1 (PDZ-RGS3) enhances canonical Wnt signaling and promotes epithelial mesenchymal transition.

ABSTRACT: The Wnt ?-catenin pathway controls numerous cellular processes including cell differentiation and cell-fate decisions. Wnt ligands engage Frizzled receptors and the low-density-lipoprotein-related protein 5/6 (LRP5/6) receptor complex leading to the recruitment of Dishevelled (Dvl) and Axin1 to the plasma membrane. Axin1 has a regulator of G-protein signaling (RGS) domain that binds adenomatous polyposis coli and G? subunits, thereby providing a mechanism by which G? subunits can affect ?-catenin levels. Here we show that Wnt signaling enhances the expression of another RGS domain-containing protein, PDZ-RGS3. Reducing PDZ-RGS3 levels impaired Wnt3a-induced activation of the canonical pathway. PDZ-RGS3 bound GSK3? and decreased its catalytic activity toward ?-catenin. PDZ-RGS3 overexpression enhanced Snail1 and led to morphological and biochemical changes reminiscent of epithelial mesenchymal transition (EMT). These results indicate that PDZ-RGS3 can enhance signals generated by the Wnt canonical pathway and that plays a pivotal role in EMT.

SUBMITTER: Shi CS 

PROVIDER: S-EPMC3460449 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature