A completely foreign receptor can mediate an interferon-γ-like response

Birgit Strobl, Velmurugesan Arulampalam, Hayaatun Is'Harc, Sally J. Newman, Jörg F. Schlaak, Diane Watling, Ana P. Costa-Pereira, Fred Schaper, Iris Behrmann, Kathleen C.F. Sheehan, Robert D. Schreiber, Friedemann Horn, Peter C. Heinrich, Ian M. Kerr

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


A tripartite receptor comprising the external region of the erythropoietin (Epo) receptor, the transmembrane and JAK-binding domains of the gp130 subunit of the interleukin-6 (IL-6) receptor, and a seven amino acid STAT1 recruitment motif (Y440) from the interferon (IFN)-γ receptor, efficiently mediates an IFN-γ-like response. An analogous completely foreign chimeric receptor in which the Y440 motif is replaced with the Y905 motif from gp130 also mediates an IFN-γ-like response, but less efficiently. The IFNGR1 signal-transducing subunit of the IFN-γ receptor is tyrosine phosphorylated through the chimeric receptors and the endogenous IL-6 and OSM receptors. Cross phosphorylation of IFNGR1 is not, however, required for the IFN-γ-like response through the chimeric receptors, nor does it mediate an IFN-γ-like response to IL-6 or OSM. The data argue strongly for modular JAK/STAT signalling and against any rigid structural organization for the 'pathways' involved. They emphasize the likely high degree of overlap between the signals generated from disparate JAK-receptor complexes and show that relatively minor changes in such complexes can profoundly affect the response.

Original languageEnglish
Pages (from-to)5431-5442
Number of pages12
JournalEMBO Journal
Issue number19
StatePublished - Oct 1 2001


  • Cytokine
  • Interferon
  • Modular signalling
  • Receptor cross phosphorylation


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