Components of a Stat recognition code: evidence for two layers of molecular selectivity

Immunity. 1995 Jun;2(6):689-97. doi: 10.1016/1074-7613(95)90013-6.


Latent and activated forms of Stat1 and Stat6 have been expressed and purified, enabling biochemical experiments relating to their functional activities. Stat1 bound to a phosphotyrosine peptide derived from the IFN gamma receptor with a KD of 50 nM, whereas Stat6 bound to an IL-4 receptor peptide with a KD of 300 nM. Stat-receptor peptide interactions were specific and dependent upon tyrosine phosphorylation. Activated forms of Stat1 and Stat6 were used to select their optimal DNA binding sites. Stat1 selected a recognition site having dyad half-sites separated by 3 bp. Stat6 selected a recognition site composed of the same dyad half-sites, yet separated by 4 bp. Chimeric Stat1-Stat6 recombinants were expressed, purified, and assayed for receptor coupling and DNA binding specificity. Such studies led to the identification of polypeptide domains that specify these activities. These observations provide a framework for understanding how different cytokines elicit distinctive patterns of gene expression.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cells, Cultured
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Fluorescence Polarization / methods
  • Humans
  • Molecular Sequence Data
  • Phosphopeptides / metabolism*
  • Protein Binding / physiology
  • Recombinant Fusion Proteins / chemistry
  • STAT1 Transcription Factor
  • STAT6 Transcription Factor
  • Trans-Activators / chemistry
  • Trans-Activators / metabolism*


  • DNA-Binding Proteins
  • Phosphopeptides
  • Recombinant Fusion Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Trans-Activators