Tyrosine dephosphorylation and concurrent inactivation of protein kinase FA/GSK-3 alpha by genistein in A431 cells

J Cell Biochem. 1994 Sep;56(1):131-41. doi: 10.1002/jcb.240560117.


Modulation of protein kinase FA/GSK-3 alpha by tyrosine phosphorylation in A431 cells was investigated. Kinase FA/GSK-3 alpha was found to exist in a highly tyrosine-phosphorylated/activated state in resting cells but could become tyrosine-dephosphorylated and inactivated down to less than 30% of control values in a concentration-dependent manner by 50-400 microM genistein (a specific tyrosine kinase inhibitor), as demonstrated by metabolic 32P-labeling of the cells followed by immunoprecipitation and two-dimensional phosphoamino acid analysis and by immunodetection in an antikinase FA/GSK-3 alpha immunoprecipitate kinase assay. Taken together, the results provide evidence that kinase FA/GSK-3 alpha may exist in a highly tyrosine-phosphorylated/activated state in resting cells which can be tyrosine-dephosphorylated and inactivated by extracellular stimulus and that tyrosine kinase(s) and/or tyrosine phosphatase(s) may play a role in the modulation of kinase FA/GSK-3 alpha activity in cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / isolation & purification
  • Brain / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
  • Calcium-Calmodulin-Dependent Protein Kinases / isolation & purification
  • Cell Line
  • Chromatography, Affinity
  • Electrophoresis, Polyacrylamide Gel
  • Genistein
  • Glycogen Synthase Kinase 3
  • Humans
  • Immunoblotting
  • Isoflavones / pharmacology*
  • Molecular Sequence Data
  • Molecular Weight
  • Peptides / chemical synthesis
  • Peptides / immunology
  • Phosphorylation
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / isolation & purification
  • Swine
  • Tumor Cells, Cultured
  • Tyrosine / metabolism


  • Antibodies
  • Isoflavones
  • Peptides
  • Tyrosine
  • Genistein
  • Protein-Tyrosine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3