Wnt3a binds to several sFRPs in the nanomolar range

Biochem Biophys Res Commun. 2007 Jun 15;357(4):1119-23. doi: 10.1016/j.bbrc.2007.04.069. Epub 2007 Apr 19.

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 beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Embryonic Stem Cells / metabolism*
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / metabolism*
  • Mice
  • Microchemistry / methods
  • Nanotechnology / methods
  • Protein Binding
  • Proto-Oncogene Proteins / metabolism*
  • Signal Transduction / physiology*
  • Wnt Proteins / metabolism*
  • Wnt3 Protein
  • Wnt3A Protein

Substances

  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Sfrp1 protein, mouse
  • Sfrp2 protein, mouse
  • Sfrp4 protein, mouse
  • Wnt Proteins
  • Wnt3 Protein
  • Wnt3A Protein
  • Wnt3a protein, mouse