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

Hai Yan, Kartik Krishnan, Andrew C. Greenland, Sanjay Gupta, Jin T.E. Lim, Robert D. Schreiber, Christian W. Schindler, John J. Krolewski

Research output: Contribution to journalArticlepeer-review

151 Scopus citations

Abstract

Interferon-α (IFNα) induces rapid tyrosine phosphorylation of its receptors, two JAK kinases and three STAT transcription factors. One kinase, p135(tyk2), is complexed with the IFNaR1 receptor, and may catalyze some of these phosphorylation events. We demonstrate that, in vitro, p135(tyk2) phosphorylates two tyrosines on IFNaR1. A phosphopeptide corresponding to the major phosphorylation site (Tyr466) binds STAT2, but not STAT1, in an SH2-dependent manner. Furthermore, only latent, non-phosphorylated STAT2 interacts with this phosphopeptide. When this phosphopeptide is introduced into permeabilized cells, the IFNα-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.

Original languageEnglish
Pages (from-to)1064-1074
Number of pages11
JournalEMBO Journal
Volume15
Issue number5
DOIs
StatePublished - Mar 1 1996

Keywords

  • Interferon
  • Signal transduction
  • Transcription factor
  • Tyrosine kinase

Fingerprint Dive into the research topics of 'Phosphorylated interferon-α receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein'. Together they form a unique fingerprint.

Cite this