Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions

Cell. 1994 Mar 11;76(5):821-8. doi: 10.1016/0092-8674(94)90357-3.


Stat91 (a 91 kd protein that acts as a signal transducer and activator of transcription) is inactive in the cytoplasm of untreated cells but is activated by phosphorylation on tyrosine in response to a number of polypeptide ligands, including interferon alpha (IFN-alpha) and IFN-gamma. We report here that the inactive Stat91 in the cytoplasm of untreated cells is a monomer and that upon IFN-gamma-induced phosphorylation it forms a stable homodimer. Only the dimer is capable of binding to a specific DNA sequence directing transcription. Through dissociation and reassociation assays, we show that dimerization of Stat91 is mediated through SH2-phosphotyrosyl peptide interactions. Dimerization involving SH2 recognition of specific phosphotyrosyl peptides may well provide a prototype for interactions among family members of STAT proteins to form different transcription complexes.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology
  • Interferons / pharmacology*
  • Ligands
  • Macromolecular Substances
  • Molecular Sequence Data
  • Molecular Weight
  • Phosphorylation
  • Phosphotyrosine
  • Protein Binding
  • STAT1 Transcription Factor
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Trans-Activators / chemistry*
  • Trans-Activators / physiology
  • Transcription Factors / chemistry*
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism


  • DNA-Binding Proteins
  • Ligands
  • Macromolecular Substances
  • STAT1 Transcription Factor
  • Trans-Activators
  • Transcription Factors
  • Phosphotyrosine
  • Tyrosine
  • Interferons