GSK-3beta-dependent phosphorylation of adenomatous polyposis coli gene product can be modulated by beta-catenin and protein phosphatase 2A complexed with Axin

Oncogene. 2000 Jan 27;19(4):537-45. doi: 10.1038/sj.onc.1203359.


Axin forms a complex with adenomatous polyposis coli gene product (APC), glycogen synthase kinase-3beta (GSK-3beta), and beta-catenin through different binding sites and downregulates beta-catenin. GSK-3beta-dependent phosphorylation of APC-(1211-2075) which has the Axin-binding site was facilitated by Axin, but that of APC-(959-1338) which lacks the Axin-binding site was not. Axin-(298-506) or Axin-(298-832), which has the GSK-3beta- and beta-catenin- but not APC-binding sites, did not enhance GSK-3beta-dependent phosphorylation of either APC-(1211-2075) or APC-(959-1338). Furthermore, beta-catenin stimulated the phosphorylation of APC-(959-1338) and APC-(1211-2075) by GSK-3beta in the presence of Axin. Consistent with these in vitro observations, expression of beta-catenin or Axin in COS cells promoted an SDS gel band shift of APC. These results indicate that APC complexed with Axin is effectively phosphorylated by GSK-3beta and that beta-catenin may modulate this phosphorylation. In addition, the heterodimeric form of protein phosphatase 2A (PP2A) directly bound to Axin, and PP2A complexed with Axin dephosphorylated APC phosphorylated by GSK-3beta. Taken together, these results suggest that GSK-3beta-dependent phosphorylation of APC can be modulated by beta-catenin and PP2A complexed with Axin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli Protein
  • Animals
  • Axin Protein
  • Binding Sites
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Chlorocebus aethiops
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Gene Expression Regulation
  • Genes, APC*
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinases
  • L Cells
  • Macromolecular Substances
  • Mice
  • Peptide Fragments / metabolism
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Protein Phosphatase 2
  • Protein Processing, Post-Translational*
  • Proteins / metabolism*
  • Recombinant Fusion Proteins / biosynthesis
  • Repressor Proteins*
  • Trans-Activators*
  • beta Catenin


  • Adenomatous Polyposis Coli Protein
  • Axin Protein
  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • Macromolecular Substances
  • Peptide Fragments
  • Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Trans-Activators
  • beta Catenin
  • Glycogen Synthase Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2