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.
D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; D002460:Cell Line; D002850:Chromatography, Gel; D003598:Cytoskeletal Proteins / Q000502:physiology*; D000072261:Dishevelled Proteins; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D008845:Microinjections; D018613:Microscopy, Confocal; D008957:Models, Genetic; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D010957:Plasmids; D011506:Proteins / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013997:Time Factors; D015534:Trans-Activators; D014162:Transfection; D051176:beta Catenin