Gene interactions and pathways from curated databases and text-mining
Nature structural & molecular biology 2007, PMID: 17529994

The DIX domain of Dishevelled confers Wnt signaling by dynamic polymerization.

Schwarz-Romond, Thomas; Fiedler, Marc; Shibata, Naoki; Butler, P Jonathan G; Kikuchi, Akira; Higuchi, Yoshiki; Bienz, Mariann

The Wnt signaling pathway controls numerous cell fates in animal development and is also a major cancer pathway. Dishevelled (Dvl) transduces the Wnt signal by interacting with the cytoplasmic Axin complex. Dvl and Axin each contain a DIX domain whose molecular properties and structure are unknown. Here, we demonstrate that the DIX domain of Dvl2 mediates dynamic polymerization, which is essential for the signaling activity of Dvl2. The purified domain polymerizes gradually, reversibly and in a concentration dependent manner, ultimately forming fibrils. The Axin DIX domain has a novel structural fold largely composed of beta-strands that engage in head-to-tail self-interaction to form filaments in the crystal. The DIX domain thus seems to mediate the formation of a dynamic interaction platform with a high local concentration of binding sites for transient Wnt signaling partners; this represents a previously uncharacterized mechanistic principle, signaling by reversible polymerization.

Document information provided by NCBI PubMed

Text Mining Data

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Manually curated Databases

  • Reactome Reaction: AXIN1 → LRP6 (reaction)
  • Reactome Reaction: DVL2 → GSK3B (reaction)
  • Reactome Reaction: AXIN1 → FZD1 (reaction)
  • Reactome Reaction: AMER1 → GSK3B (reaction)
  • Reactome Reaction: WNT8B → GSK3B (reaction)
  • Reactome Reaction: LRP6 → GSK3B (reaction)
  • Reactome Reaction: AXIN1 → FZD1 (indirect_complex)
  • Reactome Reaction: AXIN1 → DVL3 (indirect_complex)
  • Reactome Reaction: CSNK1A1 → CTNNB1 (reaction)
  • Reactome Reaction: WNT8A → GSK3B (reaction)
  • Reactome Reaction: AXIN1 → DVL1 (indirect_complex)
  • Reactome Reaction: WNT1 → GSK3B (reaction)
  • Reactome Reaction: AXIN1 → DVL2 (indirect_complex)
  • Reactome Reaction: AXIN1 → AMER1 (reaction)
  • Reactome Reaction: FZD2 → GSK3B (reaction)
  • Reactome Reaction: AXIN1 → FZD2 (indirect_complex)
  • Reactome Reaction: DVL3 → GSK3B (indirect_complex)
  • Reactome Reaction: AXIN1 → WNT1 (indirect_complex)
  • Reactome Reaction: AXIN1 → CSNK1A1 (reaction)
  • Reactome Reaction: DVL1 → GSK3B (reaction)
  • Reactome Reaction: AXIN1 → WNT8B (reaction)
  • Reactome Reaction: AXIN1 → WNT8A (reaction)
  • Reactome Reaction: WNT3A → GSK3B (reaction)
  • Reactome Reaction: WNT3A → GSK3B (indirect_complex)
  • Reactome Reaction: AXIN1 → WNT3A (indirect_complex)
  • Reactome Reaction: AMER1 → CTNNB1 (reaction)
  • Reactome Reaction: APC → GSK3B (reaction)
  • Reactome Reaction: AXIN1 → WNT8A (indirect_complex)
  • Reactome Reaction: DVL2 → GSK3B (indirect_complex)
  • Reactome Reaction: WNT1 → GSK3B (indirect_complex)
  • Reactome Reaction: AXIN1 → APC (reaction)
  • Reactome Reaction: DVL3 → GSK3B (reaction)
  • Reactome Reaction: WNT8A → GSK3B (indirect_complex)
  • Reactome Reaction: FZD2 → GSK3B (indirect_complex)
  • Reactome Reaction: AXIN1 → LRP6 (indirect_complex)
  • Reactome Reaction: CTNNB1 → GSK3B (reaction)
  • Reactome Reaction: WNT8B → GSK3B (indirect_complex)
  • Reactome Reaction: AXIN1 → CTNNB1 (reaction)
  • Reactome Reaction: AXIN1 → WNT8B (indirect_complex)
  • Reactome Reaction: AXIN1 → DVL2 (reaction)
  • Reactome Reaction: AXIN1 → DVL3 (reaction)
  • Reactome Reaction: AXIN1 → DVL1 (reaction)
  • Reactome Reaction: AXIN1 → WNT1 (reaction)
  • Reactome Reaction: DVL1 → GSK3B (indirect_complex)
  • Reactome Reaction: FZD1 → GSK3B (indirect_complex)
  • Reactome Reaction: AXIN1 → WNT3A (reaction)
  • Reactome Reaction: CSNK1A1 → APC (reaction)
  • Reactome Reaction: CSNK1A1 → AMER1 (reaction)
  • Reactome Reaction: APC → CTNNB1 (reaction)
  • Reactome Reaction: LRP6 → GSK3B (indirect_complex)
  • Reactome Reaction: CSNK1A1 → GSK3B (reaction)
  • Reactome Reaction: AXIN1 → FZD2 (reaction)
  • Reactome Reaction: FZD1 → GSK3B (reaction)
  • Reactome Reaction: AMER1 → APC (reaction)
In total, 34 gene pairs are associated to this article in curated databases