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

Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11196-200. doi: 10.1073/pnas.94.21.11196.


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

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • COS Cells
  • Cattle
  • Cysteine*
  • Cytoskeletal Proteins / biosynthesis*
  • Embryo, Nonmammalian
  • Glycoproteins*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Proteins / chemistry
  • Proteins / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Recombinant Proteins / biosynthesis
  • Signal Transduction*
  • Trans-Activators*
  • Transfection
  • Wnt Proteins
  • Wnt1 Protein
  • Xenopus
  • Xenopus Proteins
  • Zebrafish Proteins*
  • beta Catenin


  • CTNNB1 protein, Xenopus
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Glycoproteins
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Trans-Activators
  • WD repeat containing planar cell polarity effector
  • WNT1 protein, Xenopus
  • WNT1 protein, human
  • Wnt Proteins
  • Wnt1 Protein
  • Xenopus Proteins
  • Zebrafish Proteins
  • beta Catenin
  • wnt8a protein, Xenopus
  • Cysteine