Axin, a negative regulator of the wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of beta-catenin

J Biol Chem. 1998 May 1;273(18):10823-6. doi: 10.1074/jbc.273.18.10823.

Abstract

The regulators of G protein signaling (RGS) domain of Axin, a negative regulator of the Wnt signaling pathway, made a complex with full-length adenomatous polyposis coli (APC) in COS, 293, and L cells but not with truncated APC in SW480 or DLD-1 cells. The RGS domain directly interacted with the region containing the 20-amino acid repeats but not with that containing the 15-amino acid repeats of APC, although both regions are known to bind to beta-catenin. In the region containing seven 20-amino acid repeats, the region containing the latter five repeats bound to the RGS domain of Axin. Axin and beta-catenin simultaneously interacted with APC. Furthermore, Axin stimulated the degradation of beta-catenin in COS cells. Taken together with our recent observations that Axin directly interacts with glycogen synthase kinase-3beta (GSK-3beta) and beta-catenin and that it promotes GSK-3beta-dependent phosphorylation of beta-catenin, these results suggest that Axin, APC, GSK-3beta, and beta-catenin make a tetrameric complex, resulting in the regulation of the stabilization of beta-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein
  • Animals
  • Axin Protein
  • Cell Line
  • Cytoskeletal Proteins / metabolism*
  • GTPase-Activating Proteins
  • Humans
  • Protein Binding
  • Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • Repressor Proteins*
  • Signal Transduction*
  • Trans-Activators*
  • beta Catenin

Substances

  • Adenomatous Polyposis Coli Protein
  • Axin Protein
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • GTPase-Activating Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Trans-Activators
  • beta Catenin