Glycogen synthase kinase 3 phosphorylates Jun family members in vitro and negatively regulates their transactivating potential in intact cells

Oncogene. 1993 Apr;8(4):833-40.

Abstract

Expression of immediate-early genes involving the 12-O-tetradecanoyl phorbol 13-acetate (TPA)-responsive element (TRE) is modulated by post-translational modification of pre-existing activator protein 1 (AP-1) constituents. One of the components of AP-1, c-Jun, has been shown to be phosphorylated by glycogen synthase kinase 3 (GSK-3) in vitro in a region proximal to the DNA-binding domain, resulting in decreased DNA binding. Here, we have used transient transfection to show that AP-1 activity is inhibitable by coexpression of GSK-3 in intact cells. Furthermore, we show that the c-Jun-related proteins JunD and JunB are subject to similar regulation by GSK-3 in intact cells. Comparison of tryptic phosphopeptide maps of the three Jun proteins incubated with GSK-3 in vitro with maps of the same proteins immunoprecipitated from 32P-labelled cells indicates similar sites of phosphorylation. Together, these data support the hypothesis that GSK-3 is an important regulator of AP-1 activity in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Line
  • Chlorocebus aethiops
  • Glycogen Synthase Kinases
  • In Vitro Techniques
  • Mice
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / metabolism
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Recombinant Proteins / metabolism
  • Transcriptional Activation*

Substances

  • Peptides
  • Phosphoproteins
  • Proto-Oncogene Proteins c-jun
  • Recombinant Proteins
  • Protein Kinases
  • Glycogen Synthase Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases