Activation of protein kinase C decreases phosphorylation of c-Jun at sites that negatively regulate its DNA-binding activity

Cell. 1991 Feb 8;64(3):573-84. doi: 10.1016/0092-8674(91)90241-p.


In resting human epithelial and fibroblastic cells, c-Jun is phosphorylated on serine and threonine at five sites, three of which are phosphorylated in vitro by glycogen synthase kinase 3 (GSK-3). These three sites are nested within a single tryptic peptide located just upstream of the basic region of the c-Jun DNA-binding domain (residues 227-252). Activation of protein kinase C results in rapid, site-specific dephosphorylation of c-Jun at one or more of these three sites and is coincident with increased AP-1-binding activity. Phosphorylation of recombinant human c-Jun proteins in vitro by GSK-3 decreases their DNA-binding activity. Mutation of serine 243 to phenylalanine blocks phosphorylation of all three sites in vivo and increases the inherent trans-activation ability of c-Jun at least 10-fold. We propose that c-Jun is present in resting cells in a latent, phosphorylated form that can be activated by site-specific dephosphorylation in response to protein kinase C activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Calcium-Calmodulin-Dependent Protein Kinases
  • DNA Mutational Analysis
  • DNA-Binding Proteins / metabolism*
  • Enzyme Activation
  • Glycogen Synthase Kinases
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism*
  • Oligonucleotides / chemistry
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Phosphoserine / metabolism
  • Protein Binding
  • Protein Kinase C / metabolism*
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-jun
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Nuclear Proteins
  • Oligonucleotides
  • Phosphoproteins
  • Proto-Oncogene Proteins c-jun
  • Transcription Factors
  • Phosphoserine
  • Protein Kinases
  • Glycogen Synthase Kinases
  • Protein Kinase C
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Tetradecanoylphorbol Acetate