Transcription factor AP-2 activity is modulated by protein kinase A-mediated phosphorylation

FEBS Lett. 1999 Feb 5;444(1):27-31. doi: 10.1016/s0014-5793(99)00021-6.

Abstract

We recently reported that APOE promoter activity is stimulated by cAMP, this effect being mediated by factor AP-2 [Garcia et al. (1996) J. Neurosci. 16, 7550-7556]. Here, we study whether cAMP-induced phosphorylation modulates the activity of AP-2. Recombinant AP-2 was phosphorylated in vitro by protein kinase A (PKA) at Ser239. Mutation of Ser239 to Ala abolished in vitro phosphorylation of AP-2 by PKA, but not the DNA binding activity of AP-2. Cotransfection studies showed that PKA stimulated the effect of AP-2 on the APOE promoter, but not that of the S239A mutant. Therefore, cAMP may modulate AP-2 activity by PKA-induced phosphorylation of this factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Apolipoproteins E / genetics
  • Binding Sites / radiation effects
  • Cyclic AMP / physiology
  • Cyclic AMP-Dependent Protein Kinases / genetics
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Oligonucleotide Probes / metabolism
  • Oligopeptides / pharmacology
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / pharmacology
  • Phosphorylation / drug effects
  • Promoter Regions, Genetic / genetics
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / isolation & purification
  • Recombinant Fusion Proteins / metabolism
  • Sequence Deletion
  • Serine / genetics
  • Serine / metabolism
  • Serine / physiology
  • Transcription Factor AP-2
  • Transcription Factors / genetics
  • Transcription Factors / isolation & purification
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Transfection
  • Tumor Cells, Cultured
  • Ultraviolet Rays

Substances

  • Apolipoproteins E
  • DNA-Binding Proteins
  • Oligonucleotide Probes
  • Oligopeptides
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Transcription Factor AP-2
  • Transcription Factors
  • Serine
  • kemptide
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases