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

By M. Kishida, S. Hino, T. Michiue, Hideki Yamamoto, S. Kishida, A. Fukui, Makoto Asashima, A. Kikuchi. Journal of Biological Chemistry, 2001

116 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3c957f8b946363873b04b800a756bfd769f237bd

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In Molecular Biology

1. Matthias Mann
2. Jens S. Andersen
3. B. Doble
4. J. Woodgett
5. H. Varmus
6. Liang Schweizer
7. F. Cong
8. Jüergen Cox

Citations in the corpus

• Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. (2002, background): “On the other hand, upon confronting a Wnt signal, CKI interacts and synergizes with Dvl in stabilizing -catenin (Peters et al. 1999; Kishida et al. 2001; McKay et al. 2001; Gao et al. 2002).”
• Casein Kinase Iε Modulates the Signaling Specificities of Dishevelled (2004, methodology): “Consistent with results from other labs (17, 22 , 40, 45), we find that CKIe associates with Dvl in vivo and phosphorylates Dvl in vitro (data not shown).”
• GSK-3: tricks of the trade for a multi-tasking kinase (2003, result): “Such a role contrasts with that proposed in several previous reports, which identified CKI as a positive transducer of Wnt signalling (Gao et al., 2002; Kishida et al., 2001; Lee et al., 2001; McKay et al., 2001).”