Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Cytoskeletal Proteins / metabolism*
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Frizzled Receptors
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Gene Expression Regulation / physiology
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Homeodomain Proteins / antagonists & inhibitors
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Humans
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Intercellular Signaling Peptides and Proteins
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Mice
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Microinjections
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Morphogenesis
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Proteins / antagonists & inhibitors
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Proteins / genetics
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Proteins / metabolism*
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RNA, Messenger / metabolism
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Signal Transduction / physiology*
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Trans-Activators*
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Wnt Proteins
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Xenopus Proteins
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Xenopus laevis / embryology
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Xenopus laevis / physiology
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Zebrafish Proteins
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beta Catenin
Substances
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CTNNB1 protein, Xenopus
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CTNNB1 protein, human
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CTNNB1 protein, mouse
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Cytoskeletal Proteins
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DKK1 protein, human
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DKK2 protein, human
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Dkk1 protein, mouse
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Dkk2 protein, Xenopus
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Dkk2 protein, mouse
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Frizzled Receptors
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Homeodomain Proteins
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Intercellular Signaling Peptides and Proteins
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Proteins
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RNA, Messenger
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SIA1 protein, Xenopus
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Trans-Activators
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Wnt Proteins
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Xenopus Proteins
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Zebrafish Proteins
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beta Catenin
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dkk1 protein, Xenopus
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dkk1b protein, zebrafish
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wnt8a protein, zebrafish