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Cross-regulation of the Wnt signalling pathway: a role of MAP kinases

Item Type:Editorial
Title:Cross-regulation of the Wnt signalling pathway: a role of MAP kinases
Creators Name:Behrens, J.
Abstract:The Wnt signal transduction pathway regulates various aspects of embryonal development and is involved in cancer formation. Wnts induce the stabilisation of cytosolic {beta}-catenin, which then associates with TCF transcription factors to regulate expression of Wnt-target genes. At various levels the Wnt pathway is subject to cross-regulation by other components. Recent evidence suggests that a specific MAP kinase pathway involving the MAP kinase kinase kinase TAK1 and the MAP kinase NLK counteract Wnt signalling. In particular, homologues of TAK1 and NLK, MOM-4 and LIT-1, negatively regulate Wnt-controlled cell fate decision in the early Caenorhabditis elegans embryo. Moreover, TAK1 activates NLK, which phosphorylates TCFs bound to {beta}-catenin. This blocks nuclear localization and DNA binding of TCFs, Since TAK1 is activated by TGF-{beta} and various cytokines, it might provide an entry point for regulation of the Wnt system by other pathways. In addition, alterations in TAK1-NLK might play a role in cancer.
Keywords:MAP Kinase, NLK, TAK1, Wnt Pathway, Animals
Source:Journal of Cell Science
ISSN:0021-9533
Publisher:Company of Biologists (U.K.)
Volume:113
Number:6
Page Range:911-919
Date:1 March 2000
Official Publication:http://jcs.biologists.org/cgi/content/abstract/113/6/911
PubMed:View item in PubMed

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