WNT-1 and HGF regulate GSK3 beta activity and beta-catenin signaling in mammary epithelial cells

Biochem Biophys Res Commun. 1998 Jun 29;247(3):851-8. doi: 10.1006/bbrc.1998.8888.


Wnt-1, a secreted glycoprotein, participates in development of the nervous system and contributes to mammary oncogenesis when overexpressed. We show that GSK3 activity is decreased in mouse mammary cells transformed by Wnt-1. These cells also exhibit a substantial Wnt-1 dependent increase in the uncomplexed population of beta-catenin. Wnt-1 signaling does not change the steady state level of either GSK3 alpha or GSK3 beta but instead leads to an increased association between GSK3 beta and beta-catenin. HGF/SF treatment of mouse mammary cells also leads to a transient decrease in GSK3 activity and a parallel, selective increase in the uncomplexed pool of beta-catenin. Both Wnt-1 and HGF/SF lead to nuclear accumulation of beta-catenin and activation of a LEF/Tcf responsive reporter gene. This study defines a pivotal signal transduction pathway, activated by both Wnt-1 and HGF/SF, leading to decreased GSK3 beta activity and consequently an increase in the free pool and nuclear accumulation of beta-catenin and changes in gene expression.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Differentiation / physiology
  • Cell Line
  • Cytoskeletal Proteins / metabolism*
  • DNA-Binding Proteins / metabolism
  • Genes, Reporter / genetics
  • Glycogen Synthase Kinase 3
  • Hepatocyte Growth Factor / metabolism
  • Lymphoid Enhancer-Binding Factor 1
  • Mice
  • Molecular Sequence Data
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-met / metabolism
  • Signal Transduction / physiology
  • Trans-Activators*
  • Transcription Factors / metabolism
  • Transcriptional Activation / physiology
  • Transformation, Genetic / genetics
  • Wnt Proteins
  • Wnt1 Protein
  • Zebrafish Proteins*
  • beta Catenin


  • CTNNB1 protein, mouse
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Transcription Factors
  • Wnt Proteins
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • Zebrafish Proteins
  • beta Catenin
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3