STAT3 as an adapter to couple phosphatidylinositol 3-kinase to the IFNAR1 chain of the type I interferon receptor

Science. 1997 May 30;276(5317):1418-20. doi: 10.1126/science.276.5317.1418.

Abstract

STAT (signal transducers and activators of transcription) proteins undergo cytokine-dependent phosphorylation on serine and tyrosine. STAT3, a transcription factor for acute phase response genes, was found to act as an adapter molecule in signal transduction from the type I interferon receptor. STAT3 bound to a conserved sequence in the cytoplasmic tail of the IFNAR1 chain of the receptor and underwent interferon-dependent tyrosine phosphorylation. The p85 regulatory subunit of phosphatidylinositol 3-kinase, which activates a series of serine kinases, bound to phosphorylated STAT3 and subsequently underwent tyrosine phosphorylation. Thus, STAT3 acts as an adapter to couple another signaling pathway to the interferon receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics*
  • Amino Acid Sequence
  • Androstadienes / pharmacology
  • Animals
  • Binding Sites
  • COS Cells
  • Cell Line
  • Cloning, Molecular
  • Conserved Sequence
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Membrane Proteins
  • Molecular Sequence Data
  • Phosphatidylinositol 3-Kinases
  • Phosphorylation
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Point Mutation
  • Protein Binding
  • Receptor, Interferon alpha-beta
  • Receptors, Interferon / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • STAT3 Transcription Factor
  • Signal Transduction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Tyrosine / metabolism
  • Wortmannin

Substances

  • Acute-Phase Proteins
  • Androstadienes
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Membrane Proteins
  • Receptors, Interferon
  • Recombinant Fusion Proteins
  • STAT3 Transcription Factor
  • Trans-Activators
  • Receptor, Interferon alpha-beta
  • Tyrosine
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)
  • Wortmannin