title: A completely foreign receptor can mediate an interferon-gamma-like response.
abstract: 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)-gamma receptor, efficiently mediates an IFN-gamma-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-gamma-like response, but less efficiently. The IFNGR1 signal-transducing subunit of the IFN-gamma 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-gamma-like response through the chimeric receptors, nor does it mediate an IFN-gamma-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.
authors.affiliation: Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
authors.forename: B
authors.initials: B
authors.lastname: Strobl
authors.forename: V
authors.initials: V
authors.lastname: Arulampalam
authors.forename: H
authors.initials: H
authors.lastname: Is'harc
authors.forename: S J
authors.initials: SJ
authors.lastname: Newman
authors.forename: J F
authors.initials: JF
authors.lastname: Schlaak
authors.forename: D
authors.initials: D
authors.lastname: Watling
authors.forename: A P
authors.initials: AP
authors.lastname: Costa-Pereira
authors.forename: F
authors.initials: F
authors.lastname: Schaper
authors.forename: I
authors.initials: I
authors.lastname: Behrmann
authors.forename: K C
authors.initials: KC
authors.lastname: Sheehan
authors.forename: R D
authors.initials: RD
authors.lastname: Schreiber
authors.forename: F
authors.initials: F
authors.lastname: Horn
authors.forename: P C
authors.initials: PC
authors.lastname: Heinrich
authors.forename: I M
authors.initials: IM
authors.lastname: Kerr
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D009687:Nuclear Proteins; D053633:Receptor, Interferon alpha-beta; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000096:biosynthesis / Q000378:metabolism; D000096743:Interferon gamma Receptor
chemical_list: D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D009687:Nuclear Proteins; D053633:Receptor, Interferon alpha-beta; D017467:Receptors, Erythropoietin; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000096743:Interferon gamma Receptor; C083728:MHC class II transactivator protein; C494079:STAT1 protein, human