R-spondin1 is a high affinity ligand for LRP6 and induces LRP6 phosphorylation and β-catenin signaling

Qiou Wei, Chika Yokota, Mikhail V. Semenov, Brad Doble, Jim Woodgett, Xi He

Research output: Contribution to journalArticlepeer-review

161 Scopus citations

Abstract

R-spondin proteins are newly identified secreted molecules that activate β-catenin signaling. However, the mechanism of R-spondin action and its relationship with Wnt signaling remain unclear. Here we show that human R-spondin1 (hRspo1) is a high affinity ligand for the Wnt co-receptor LRP6 (Kd = 1.2 nM). hRspo1 induces glycogen synthase kinase 3-dependent phosphorylation and activation of LRP6. DKK1, an LRP6 antagonist, inhibits hRspo1-induced LRP6 phosphorylation. We further demonstrate that hRspo1 synergizes with Frizzled5 in Xenopus axis induction assays and induces the phosphorylation of Dishevelled, a cytoplasmic component downstream of Frizzled function. Our study reveals interesting similarity and distinction between Wnt and R-spondin signaling.

Original languageEnglish
Pages (from-to)15903-15911
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number21
DOIs
StatePublished - May 25 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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