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Curr Biol December 1, 2000; 10 (24): 1611-4.

Mutual antagonism between dickkopf1 and dickkopf2 regulates Wnt/beta-catenin signalling.

Wu W , Glinka A , Delius H , Niehrs C .

Wnts are secreted glycoproteins implicated in diverse processes during embryonic patterning in metazoans. They signal through seven-transmembrane receptors of the Frizzled (Fz) family [1] to stabilise beta-catenin [2]. Wnts are antagonised by several extracellular inhibitors including the product of the dickkopf1 (dkk1) gene, which was identified in Xenopus embryos and is a member of a multigene family. The dkk1 gene acts upstream of the Wnt pathway component dishevelled but its mechanism of action is unknown [3]. Although the function of Dkk1 as a Wnt inhibitor in vertebrates is well established [3-6], the effect of other Dkks on the Wnt/beta-catenin pathway is unclear. Here, we report that a related family member, Dkk2, activates rather than inhibits the Wnt/beta-catenin signalling pathway in Xenopus embryos. Dkk2 strongly synergised with Wnt receptors of the Fz family to induce Wnt signalling responses. The study identifies Dkk2 as a secreted molecule that is able to activate Wnt/beta-catenin signalling. The results suggest that a coordinated interplay between inhibiting dkk1 and activating dkk2 can modulate Fz signalling.

PubMed ID: 11137016
Article link: Curr Biol

Genes referenced: ag1 chrd.1 dkk1 dkk2 dkk3 dvl2 fzd1 fzd2 fzd3 fzd4 fzd5 fzd6 fzd7 fzd8 gsc ncam1 nog ptk2b sia1 sox17a sox17b.1 tbxt ventx1.1 wnt5a wnt8a

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References :
Zorn, Wnt signalling: antagonistic Dickkopfs. 2001, Pubmed

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