Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein

Science. 1992 Dec 11;258(5089):1808-12. doi: 10.1126/science.1281555.


Interferon-gamma (IFN-gamma) induces the transcription of the gene encoding a guanylate binding protein by activating a latent cytoplasmic factor, GAF (gamma-activated factor). GAF is translocated to the nucleus and binds a DNA element, the gamma-activated site. Through cross-linking and the use of specific antibodies GAF was found to be a 91-kilodalton DNA binding protein that was previously identified as one of four proteins in interferon-stimulated gene factor-3 (ISGF-3), a transcription complex activated by IFN-alpha. The IFN-gamma-dependent activation of the 91-kilodalton DNA binding protein required cytoplasmic phosphorylation of the protein on tyrosine. The 113-kilodalton ISGF-3 protein that is phosphorylated in response to IFN-alpha was not phosphorylated nor translocated to the nucleus in response to IFN-gamma. Thus the two different ligands result in tyrosine phosphorylation of different combinations of latent cytoplasmic transcription factors that then act at different DNA binding sites.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Electrophoresis, Gel, Two-Dimensional
  • Electrophoresis, Polyacrylamide Gel
  • GTP-Binding Proteins / genetics*
  • Gene Expression Regulation / drug effects
  • Interferon-alpha / pharmacology
  • Interferon-gamma / pharmacology*
  • Models, Biological
  • Molecular Sequence Data
  • Molecular Weight
  • Oligodeoxyribonucleotides
  • Phosphorylation
  • Phosphotyrosine
  • Promoter Regions, Genetic
  • STAT1 Transcription Factor
  • Signal Transduction / drug effects
  • Trans-Activators*
  • Transcription, Genetic* / drug effects
  • Tyrosine / analogs & derivatives
  • Tyrosine / analysis


  • DNA-Binding Proteins
  • Interferon-alpha
  • Oligodeoxyribonucleotides
  • STAT1 Transcription Factor
  • Trans-Activators
  • Phosphotyrosine
  • Tyrosine
  • Interferon-gamma
  • GTP-Binding Proteins