Interaction of Axin and Dvl-2 proteins regulates Dvl-2-stimulated TCF-dependent transcription

Axin promotes the phosphorylation of beta-catenin by GSK-3 beta, leading to beta-catenin degradation. Wnt signals interfere with beta-catenin turnover , resulting in enhanced transcription of target genes through the increased formation of beta-catenin complexes containing TCF transcription factors. Little is known about how GSK-3 beta-mediated beta-catenin turnover is regu lated in response to Wnt signals. We have explored the relationship between Axin and Dvl-2, a member of the Dishevelled family of proteins that functi on upstream of GSK-3 beta, Expression of Dvl-2 activated TCF-dependent tran scription. This was blocked by co-expression of GSK-3 beta or Axin, Express ion of a 59 amino acid GSK-3 beta-binding region from Axin strongly activat ed transcription in the absence of an upstream signal. Introduction of a po int mutation into full-length Axin that prevented GSK-3 beta binding also g enerated a transcriptional activator. When co-expressed, Axin and Dvl-2 co- localized within expressing cells. When Dvl-2 localization was altered usin g a C-terminal CAAX motif, Axin was also redistributed, suggesting a close association between the two proteins, a conclusion supported by co-immunopr ecipitation data. Deletion analysis suggested that Dvl-association determin ants within Axin were contained between residues 603 and 810, The associati on of Axin with Dvl-2 may be important in the transmission of Wnt signals f rom Dvl-2 to GSK-3 beta.