Secreted frizzled-related protein 2 (sFRP2) redirects non-canonical Wnt signaling from Fz7 to Ror2 during vertebrate gastrulation
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 (sF...
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| Hauptverfasser: | , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
April 20, 2016
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| In: |
The journal of biological chemistry
Year: 2016, Jahrgang: 291, Heft: 26, Pages: 13730-13742 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M116.733766 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1074/jbc.M116.733766 Verlag, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919455/ 
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| Verfasserangaben: | Eva-Maria Brinkmann, Benjamin Mattes, Rahul Kumar, Anja I. H. Hagemann, Dietmar Gradl, Steffen Scholpp, Herbert Steinbeisser, Lilian T. Kaufmann, and Suat Özbek |
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| 245 | 1 | 0 | |a Secreted frizzled-related protein 2 (sFRP2) redirects non-canonical Wnt signaling from Fz7 to Ror2 during vertebrate gastrulation |c Eva-Maria Brinkmann, Benjamin Mattes, Rahul Kumar, Anja I. H. Hagemann, Dietmar Gradl, Steffen Scholpp, Herbert Steinbeisser, Lilian T. Kaufmann, and Suat Özbek |
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| 520 | |a 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. | ||
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