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Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein.

Interferon-alpha (IFN alpha) induces rapid tyrosine phosphorylation of its receptors, two JAK kinases and three STAT transcription factors. One kinase, p135tyk2, is complexed with the IFNaR1 receptor, and may catalyze some of these phosphorylation events. We demonstrate that, in vitro, p135tyk2 phosphorylates two tyrosines on IFNaR1. A phosphopeptide corresponding to the major phosphorylation site (Tyr466) binds STAT2, but not STAT1, in an SH-2-dependent manner. Furthermore, only latent, non-phosphorylated STAT2 interacts with this phosphopeptide. When this phosphopeptide is introduced into permeabilized cells, the IFN alpha-dependent tyrosine phosphorylation of both STATs is blocked. Finally, mutant versions of IFNaR1, in which Tyr466 is changed to phenylalanine, can act in a dominant negative manner to inhibit phosphorylation of STAT2. These observations are consistent with a model in which IFNaR1 mediates the interaction between JAK kinases and the STAT transcription factors.

Pubmed ID: 8605876


  • Yan H
  • Krishnan K
  • Greenlund AC
  • Gupta S
  • Lim JT
  • Schreiber RD
  • Schindler CW
  • Krolewski JJ


The EMBO journal

Publication Data

March 1, 1996

Associated Grants

  • Agency: NCI NIH HHS, Id: CA56862

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • DNA-Binding Proteins
  • Humans
  • In Vitro Techniques
  • Interferon-alpha
  • Models, Biological
  • Molecular Sequence Data
  • Molecular Weight
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Protein Conformation
  • Protein-Tyrosine Kinases
  • Proteins
  • Receptor, Interferon alpha-beta
  • Receptors, Interferon
  • Recombinant Proteins
  • STAT1 Transcription Factor
  • STAT2 Transcription Factor
  • Signal Transduction
  • TYK2 Kinase
  • Trans-Activators
  • src Homology Domains