dc.contributor.author | Brinkmann, E-M | |
dc.contributor.author | Mattes, B | |
dc.contributor.author | Kumar, R | |
dc.contributor.author | Hagemann, AIH | |
dc.contributor.author | Gradl, D | |
dc.contributor.author | Scholpp, S | |
dc.contributor.author | Steinbeisser, H | |
dc.contributor.author | Kaufmann, LT | |
dc.contributor.author | Özbek, S | |
dc.date.accessioned | 2017-08-08T11:45:35Z | |
dc.date.issued | 2016-04-29 | |
dc.description.abstract | Convergent extension movements during vertebrate gastrulation require a balanced activity of non-canonical Wnt signaling pathways, but the factors regulating this interplay on the molecular level are poorly characterized. Here we show that sFRP2, a member of the secreted frizzled-related protein (sFRP) family, is required for morphogenesis and papc expression during Xenopus gastrulation. We further provide evidence that sFRP2 redirects non-canonical Wnt signaling from Frizzled 7 (Fz7) to the receptor tyrosine kinase-like orphan receptor 2 (Ror2). During this process, sFRP2 promotes Ror2 signal transduction by stabilizing Wnt5a-Ror2 complexes at the membrane, whereas it inhibits Fz7 signaling, probably by blocking Fz7 receptor endocytosis. The cysteine-rich domain of sFRP2 is sufficient for Ror2 activation, and related sFRPs can substitute for this function. Notably, direct interaction of the two receptors via their cysteine-rich domains also promotes Ror2-mediated papc expression but inhibits Fz7 signaling. We propose that sFRPs can act as a molecular switch, channeling the signal input for different non-canonical Wnt pathways during vertebrate gastrulation. | en_GB |
dc.identifier.citation | Vol. 291 (26), pp. 13730 - 13742 | en_GB |
dc.identifier.doi | 10.1074/jbc.M116.733766 | |
dc.identifier.uri | http://hdl.handle.net/10871/28815 | |
dc.language.iso | en | en_GB |
dc.publisher | American Society for Biochemistry and Molecular Biology | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/27129770 | en_GB |
dc.subject | Fz7 | en_GB |
dc.subject | Ror2 | en_GB |
dc.subject | Wnt signaling | en_GB |
dc.subject | Xenopus | en_GB |
dc.subject | development | en_GB |
dc.subject | embryo | en_GB |
dc.subject | papc | en_GB |
dc.subject | sFRP2 | en_GB |
dc.subject | zebrafish | en_GB |
dc.subject | Animals | en_GB |
dc.subject | Gastrula | en_GB |
dc.subject | HEK293 Cells | en_GB |
dc.subject | Humans | en_GB |
dc.subject | Membrane Proteins | en_GB |
dc.subject | Receptor Tyrosine Kinase-like Orphan Receptors | en_GB |
dc.subject | Receptors, Cell Surface | en_GB |
dc.subject | Receptors, G-Protein-Coupled | en_GB |
dc.subject | Wnt Signaling Pathway | en_GB |
dc.subject | Wnt-5a Protein | en_GB |
dc.subject | Xenopus Proteins | en_GB |
dc.subject | Xenopus laevis | en_GB |
dc.subject | Zebrafish | en_GB |
dc.subject | Zebrafish Proteins | en_GB |
dc.title | Secreted Frizzled-related Protein 2 (sFRP2) Redirects Non-canonical Wnt Signaling from Fz7 to Ror2 during Vertebrate Gastrulation | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2017-08-08T11:45:35Z | |
exeter.place-of-publication | United States | en_GB |
dc.description | This is the final version of the article. Available from American Society for Biochemistry and Molecular Biology via the DOI in this record. | en_GB |
dc.identifier.journal | Journal of Biological Chemistry | en_GB |