Wnt3a binds to several sFRPs in the nanomolar range |
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Authors: | Wawrzak Danuta Métioui Mourad Willems Erik Hendrickx Marijke de Genst Erwin Leyns Luc |
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Affiliation: | a Laboratory for Cell Genetics, Vrije Universiteit Brussel (VUB), Pleinlaan 2, B-1050 Brussels, Belgium b Department of Cellular and Molecular Interactions (VIB), Vrije Universiteit Brussel (VUB), Pleinlaan 2, B-1050 Brussels, Belgium |
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Abstract: | Secreted Frizzled-related proteins (sFRPs) are modulators of the Wnt signaling pathway that plays important roles in both embryogenesis and oncogenesis. sFRPs have been proposed to antagonize Wnt activity by binding to Wnts. However, the affinity of this binding is unknown. Here we show, using surface plasmon resonance and purified proteins, that sFRP1, sFRP2, sFRP4, and Frzb bind directly to Wnt3a with affinities in the nanomolar range. However, only sFRP1 and sFRP2 antagonize Wnt3a activity by blocking Wnt3a induced β-catenin accumulation in L cells. Furthermore, sFRP2, but not Frzb, antagonizes Wnt3a signaling in an ES cell model of mesoderm differentiation. These results provide the first measurement of binding affinity of sFRPs for a Wnt, which together with the measurement of antagonistic activity of sFRPs could help understand how sFRPs regulate Wnt signaling. |
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Keywords: | SPR, surface plasmon resonance ES cells, mouse embryonic stem cells EB, embryoid bodies |
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