DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate beta-catenin stability.
The N-terminal region of Dvl-1 (a mammalian Dishevelled homolog) shares 37% identity with the C-terminal region of Axin, and this related region is named the DIX domain. The functions of the DIX domains of Dvl-1 and Axin were investigated. By yeast two-hybrid screening, the DIX domain of Dvl-1 was found ... to interact with Dvl-3, a second mammalian Dishevelled relative. The DIX domains of Dvl-1 and Dvl-3 directly bound one another. Furthermore, Dvl-1 formed a homo-oligomer. Axin also formed a homo-oligomer, and its DIX domain was necessary. The N-terminal region of Dvl-1, including its DIX domain, bound to Axin directly. Dvl-1 inhibited Axin-promoted glycogen synthase kinase 3beta-dependent phosphorylation of beta-catenin, and the DIX domain of Dvl-1 was required for this inhibitory activity. Expression of Dvl-1 in L cells induced the nuclear accumulation of beta-catenin, and deletion of the DIX domain abolished this activity. Although expression of Axin in SW480 cells caused the degradation of beta-catenin and reduced the cell growth rate, expression of an Axin mutant that lacks the DIX domain did not affect the level of beta-catenin or the growth rate. These results indicate that the DIX domains of Dvl-1 and Axin are important for protein-protein interactions and that they are necessary for the ability of Dvl-1 and Axin to regulate the stability of beta-catenin.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Cell Line, Chromatography, Gel, Cytoskeletal Proteins, Dose-Response Relationship, Drug, Escherichia coli, Fluorescent Antibody Technique, Microinjections, Microscopy, Confocal, Models, Genetic, Phosphoproteins, Phosphorylation, Plasmids, Proteins, Proto-Oncogene Proteins c-myc, Repressor Proteins, Saccharomyces cerevisiae, Time Factors, Trans-Activators, Transfection, beta Catenin
Adaptor Proteins, Signal Transducing, Cell Line, Chromatography, Gel, Cytoskeletal Proteins, Dose-Response Relationship, Drug, Escherichia coli, Fluorescent Antibody Technique, Microinjections, Microscopy, Confocal, Models, Genetic, Phosphoproteins, Phosphorylation, Plasmids, Proteins, Proto-Oncogene Proteins c-myc, Repressor Proteins, Saccharomyces cerevisiae, Time Factors, Trans-Activators, Transfection, beta Catenin
Mol. Cell. Biol.
Date: Jun. 01, 1999
PubMed ID: 10330181
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