The cysteine-rich frizzled domain of Frzb-1 is required and sufficient for modulation of Wnt signaling

• DOI: 10.1073/pnas.94.21.11196
• Publication Date: 2002-07-26T14:35:50Z
• Authors: Keming Lin; Shouwen Wang; Martin A. Julius; Jan Kitajewski; Malcolm Moos; Frank P. Luyten
• Keywords: LRP6; LRP5; Dishevelled

Convincing evidence has accumulated to identify the Frizzled proteins as receptors for Wnt growth factors. In parallel, a number of secreted frizzled-like with conserved N-terminal frizzled motif have been identified. One these proteins, Frzb-1, binds Wnt-1 and Xwnt-8 antagonizes signaling in Xenopus embryos. Here we report that Frzb-1 blocks induced cytosolic accumulation β-catenin, key component pathway, human embryonic kidney cells. Structure/function analysis reveals complete removal domain abolishes Wnt-1/Frzb-1 protein interaction inhibition mediated axis duplication contrast, C-terminal portion molecule preserves both Frzb-Wnt binding functional signaling. Partial deletions cysteine-rich maintain interaction, but is lost. Taken together, findings support conclusion necessary sufficient activities. Interestingly, does not block Wnt-5A assay, even though coimmunoprecipitates suggesting coimmunoprecipitation necessarily imply function.