Wnt-induced dephosphorylation of axin releases beta-catenin from the axin complex

Genes Dev. 1999 Jul 15;13(14):1768-73. doi: 10.1101/gad.13.14.1768.

Abstract

The stabilization of beta-catenin is a key regulatory step during cell fate changes and transformations to tumor cells. Several interacting proteins, including Axin, APC, and the protein kinase GSK-3beta are implicated in regulating beta-catenin phosphorylation and its subsequent degradation. Wnt signaling stabilizes beta-catenin, but it was not clear whether and how Wnt signaling regulates the beta-catenin complex. Here we show that Axin is dephosphorylated in response to Wnt signaling. The dephosphorylated Axin binds beta-catenin less efficiently than the phosphorylated form. Thus, Wnt signaling lowers Axin's affinity for beta-catenin, thereby disengaging beta-catenin from the degradation machinery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axin Protein
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Line
  • Cytoskeletal Proteins / metabolism*
  • Glycogen Synthase Kinase 3
  • Phosphorylation
  • Protein Binding
  • Proteins / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Repressor Proteins*
  • Signal Transduction
  • Trans-Activators*
  • Wnt Proteins
  • Zebrafish Proteins*
  • beta Catenin

Substances

  • Axin Protein
  • Cytoskeletal Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Trans-Activators
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3