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dc.contributor.authorKagermeier-Schenk, B
dc.contributor.authorWehner, D
dc.contributor.authorOzhan-Kizil, G
dc.contributor.authorYamamoto, H
dc.contributor.authorLi, J
dc.contributor.authorKirchner, K
dc.contributor.authorHoffmann, C
dc.contributor.authorStern, Peter L
dc.contributor.authorKikuchi, A
dc.contributor.authorSchambony, A
dc.contributor.authorWeidinger, G
dc.date.accessioned2012-06-07T10:29:11Z
dc.date.available2012-06-07T10:29:11Z
dc.date.issued2011-12-13
dc.identifier.citationWaif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization. 2011, 21 (6):1129-43 Dev Cellen_GB
dc.identifier.issn1878-1551
dc.identifier.pmid22100263
dc.identifier.doi10.1016/j.devcel.2011.10.015
dc.identifier.urihttp://hdl.handle.net/10541/227812
dc.description.abstractWnt proteins can activate distinct signaling pathways, but little is known about the mechanisms regulating pathway selection. Here we show that the metastasis-associated transmembrane protein Wnt-activated inhibitory factor 1 (Waif1/5T4) interferes with Wnt/β-catenin signaling and concomitantly activates noncanonical Wnt pathways. Waif1 inhibits β-catenin signaling in zebrafish and Xenopus embryos as well as in mammalian cells, and zebrafish waif1a acts as a direct feedback inhibitor of wnt8-mediated mesoderm and neuroectoderm patterning during zebrafish gastrulation. Waif1a binds to the Wnt coreceptor LRP6 and inhibits Wnt-induced LRP6 internalization into endocytic vesicles, a process that is required for pathway activation. Thus, Waif1a modifies Wnt/β-catenin signaling by regulating LRP6 subcellular localization. In addition, Waif1a enhances β-catenin-independent Wnt signaling in zebrafish embryos and Xenopus explants by promoting a noncanonical function of Dickkopf1. These results suggest that Waif1 modulates pathway selection in Wnt-receiving cells.
dc.language.isoenen
dc.rightsArchived with thanks to Developmental cellen_GB
dc.subject.meshAnimals
dc.subject.meshAnimals, Genetically Modified
dc.subject.meshCell Line
dc.subject.meshFrizzled Receptors
dc.subject.meshGene Expression Regulation, Developmental
dc.subject.meshHumans
dc.subject.meshIntercellular Signaling Peptides and Proteins
dc.subject.meshLow Density Lipoprotein Receptor-Related Protein-6
dc.subject.meshMesoderm
dc.subject.meshMolecular Sequence Data
dc.subject.meshNeural Plate
dc.subject.meshRecombinant Proteins
dc.subject.meshWnt Signaling Pathway
dc.subject.meshXenopus
dc.subject.meshXenopus Proteins
dc.subject.meshZebrafish
dc.subject.meshZebrafish Proteins
dc.subject.meshbeta Catenin
dc.titleWaif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization.en
dc.typeArticleen
dc.contributor.departmentBiotechnology Center and Center for Regenerative Therapies, Technische Universität Dresden, Tatzberg 47, 01307 Dresden, Germany.en_GB
dc.identifier.journalDevelopmental Cellen_GB
html.description.abstractWnt proteins can activate distinct signaling pathways, but little is known about the mechanisms regulating pathway selection. Here we show that the metastasis-associated transmembrane protein Wnt-activated inhibitory factor 1 (Waif1/5T4) interferes with Wnt/β-catenin signaling and concomitantly activates noncanonical Wnt pathways. Waif1 inhibits β-catenin signaling in zebrafish and Xenopus embryos as well as in mammalian cells, and zebrafish waif1a acts as a direct feedback inhibitor of wnt8-mediated mesoderm and neuroectoderm patterning during zebrafish gastrulation. Waif1a binds to the Wnt coreceptor LRP6 and inhibits Wnt-induced LRP6 internalization into endocytic vesicles, a process that is required for pathway activation. Thus, Waif1a modifies Wnt/β-catenin signaling by regulating LRP6 subcellular localization. In addition, Waif1a enhances β-catenin-independent Wnt signaling in zebrafish embryos and Xenopus explants by promoting a noncanonical function of Dickkopf1. These results suggest that Waif1 modulates pathway selection in Wnt-receiving cells.


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