Domains of axin and disheveled required for interaction and function in wnt signaling

Biochem Biophys Res Commun. 2000 Oct 5;276(3):1162-9. doi: 10.1006/bbrc.2000.3607.

Abstract

Disheveled blocks the degradation of beta-catenin in response to Wnt signal by interacting with the scaffolding protein, Axin. To define this interaction in detail we undertook a mutational and binding analysis of the murine Axin and Disheveled proteins. The DIX domain of Axin was found to be important for association with Disheveled and two other regions of Axin (between residues 1-168 and 600-810) were identified that can promote the association of Axin and Disheveled. We found that the DIX domain of Disheveled is critical for association with Axin in vivo and for Disheveled activity. The Disheveled DIX domain controlled the ability of Disheveled to induce the accumulation of cytosolic beta-catenin whereas the PDZ domain was not essential to this function.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Axin Protein
  • Binding Sites
  • Cell Line
  • Cytoskeletal Proteins / metabolism
  • Cytosol / chemistry
  • Dishevelled Proteins
  • Embryo, Nonmammalian / metabolism
  • Fibroblasts
  • Fluorescent Antibody Technique
  • Humans
  • Mice
  • Phosphoproteins / chemistry*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • Repressor Proteins*
  • Sequence Deletion / genetics
  • Signal Transduction*
  • Thermodynamics
  • Trans-Activators*
  • Two-Hybrid System Techniques
  • Wnt Proteins
  • Xenopus Proteins
  • Xenopus laevis / embryology
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism
  • Zebrafish Proteins*
  • beta Catenin

Substances

  • Adaptor Proteins, Signal Transducing
  • Axin Protein
  • CTNNB1 protein, Xenopus
  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Ctnnb1 protein, rat
  • Cytoskeletal Proteins
  • Dishevelled Proteins
  • Phosphoproteins
  • Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Trans-Activators
  • Wnt Proteins
  • Xenopus Proteins
  • Zebrafish Proteins
  • axin1 protein, Xenopus
  • beta Catenin