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The ankyrin repeat protein Diversin recruits Casein kinase Iepsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling

Official URL:https://doi.org/10.1101/gad.230402
PubMed:View item in PubMed
Creators Name:Schwarz-Romond, T. and Asbrand, C. and Bakkers, J. and Kuehl, M. and Schaeffer, H.J. and Huelsken, J. and Behrens, J. and Hammerschmidt, M. and Birchmeier, W.
Journal Title:Genes & Development
Journal Abbreviation:Genes Dev
Page Range:2073-2084
Date:15 August 2002
Keywords:Signal Transduction, Embryonic Axis Formation, Planar Cell Polarity, Axin/Conductin, Diego, Animals, Mice, Zebrafish
Abstract:Wnt signals control decisive steps in development and can induce the formation of tumors. Canonical Wnt signals control the formation of the embryonic axis, and are mediated by stabilization and interaction of {beta}-catenin with Lef/Tcf transcription factors. An alternative branch of the Wnt pathway uses JNK to establish planar cell polarity in Drosophila and gastrulation movements in vertebrates. We describe here the vertebrate protein Diversin that interacts with two components of the canonical Wnt pathway, Casein kinase I{epsilon} (CKI{epsilon}) and Axin/Conductin. Diversin recruits CKI{epsilon} to the {beta}-catenin degradation complex that consists of Axin/Conductin and GSK3{beta} and allows efficient phosphorylation of {beta}-catenin, thereby inhibiting {beta}-catenin/Tcf signals. Morpholino-based gene ablation in zebrafish shows that Diversin is crucial for axis formation, which depends on {beta}-catenin signaling. Diversin is also involved in JNK activation and gastrulation movements in zebrafish. Diversin is distantly related to Diego of Drosophila, which functions only in the pathway that controls planar cell polarity. Our data show that Diversin is an essential component of the Wnt-signaling pathway and acts as a molecular switch, which suppresses Wnt signals mediated by the canonical {beta}-catenin pathway and stimulates signaling via JNK.
Publisher:Cold Spring Harbor Laboratory Press (U.S.A.)
Item Type:Article

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