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A completely foreign receptor can mediate an interferon‐γ‐like response
Author(s) -
Strobl Birgit,
Arulampalam Velmurugesan,
Is'harc Hayaatun,
Newman Sally J.,
Schlaak Jörg F.,
Watling Diane,
CostaPereira Ana P.,
Schaper Fred,
Behrmann Iris,
Sheehan Kathleen C.F.,
Schreiber Robert D.,
Horn Friedemann,
Heinrich Peter C.,
Kerr Ian M.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.19.5431
Subject(s) - biology , interferon gamma , receptor , microbiology and biotechnology , immunology , genetics , cytokine
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.