Regulator of G-Protein Signaling 3 Isoform 1 (PDZ-RGS3) Enhances Canonical Wnt Signaling and Promotes Epithelial Mesenchymal Transition |
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Authors: | Chong-Shan Shi Ning-Na Huang John H Kehrl |
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Institution: | From the B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892 |
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Abstract: | The Wnt β-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 Gα subunits, thereby providing a mechanism by which Gα subunits can affect β-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 GSK3β and decreased its catalytic activity toward β-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. |
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Keywords: | Catenin Epithelial to Mesenchymal Transition Glycogen Synthase Kinase 3 RGS Proteins Signal Transduction |
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