Synergistic Activation of the Wnt Signaling Pathway by Dvl and Casein Kinase Iε*

Although casein kinase Iε (CKIε) has been shown to regulate the Wnt signaling pathway positively, its mode of action is not clear. In this study we show that CKIε activates the Wnt signaling pathway in co-operation with Dvl. CKIε and Axin associated with different sites of Dvl, and CKIε and Dvl interacted with distinct regions on Axin. Therefore, these three proteins formed a ternary complex. Either low expression of Dvl or CKIε alone did not accumulate β-catenin, but their co-expression accumulated greatly. Dvl and CKIε activated the transcriptional activity of T cell factor (Tcf) synergistically. Although the Dvl mutant that binds to Axin but not to CKIε activated Tcf, it did not synergize with CKIε. Another Dvl mutant that does not bind to Axin did not activate Tcf irrespective of the presence of CKIε. Furthermore, Dvl and CKIε co-operatively induced axis duplication of Xenopus embryos. These results indicate that Dvl and CKIε synergistically activated the Wnt signaling pathway and that the binding of the complex of Dvl and CKIε to Axin is necessary for their synergistic action.

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