K. Itoh et al., Interaction of dishevelled and Xenopus axin-related protein is required for Wnt signal transduction, MOL CELL B, 20(6), 2000, pp. 2228-2238
Signaling by the Wnt family of secreted proteins plays an important role in
animal development and is often misregulated in carcinogenesis. Wnt signal
transduction is controlled by the rate of degradation of beta-catenin by a
complex of proteins including glycogen synthase kinase 3 (GSK3), adenomato
us polyposis coli, and Axin, Dishevelled is required for Wnt signal transdu
ction, and its activation results in stabilization of beta-catenin. However
, the biochemical events underlying this process remain largely unclear. He
re we show that Xenopus Dishevelled (Xdsh) interacts with a Xenopus Axin-re
lated protein (XARP). This interaction depends on the presence of the Dishe
velled-Axin (DIX) domains in both XARP and Xdsh. Moreover, the same domains
are essential for signal transduction through Xdsh, Finally, our data poin
t to a possible mechanism for signal transduction, in which Xdsh prevents b
eta-catenin degradation by displacing GSK3 from its complex with XARP.