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dc.contributor.authorFALLON, PADRAIC
dc.contributor.authorO'NEILL, LUKE ANTHONY JOHN
dc.date.accessioned2009-09-17T17:20:02Z
dc.date.available2009-09-17T17:20:02Z
dc.date.issued2002
dc.date.submitted2002en
dc.identifier.citationBrint, E.K., Fitzgerald, K.A., Smith, P., Coyle, A.J., Gutierrez-Ramos, J-C., Fallon, P.G. and O?Neill, L.A.J. `Characterization of signaling pathways activated by the interleukin 1 (IL-1) receptor homologue T1/ST2. A role for Jun N-terminal kinase in IL-4 induction? in Journal of Biological Chemistry, 277, (51), 2002, pp 49205 - 49211en
dc.identifier.otherYen
dc.identifier.otherY
dc.identifier.urihttp://hdl.handle.net/2262/32919
dc.descriptionPUBLISHEDen
dc.description.abstractT1/ST2 is a member of the interleukin (IL)-1 receptor superfamily, possessing three immunoglobulin domains extracellularly and a Toll/IL1R (TIR) domain intracellularly. The ligand for T1/ST2 is not known. T1/ST2 is expressed on Type 2 T helper (Th2) cells, and its role appears to be in the regulation of Th2 cell function. Here, we have investigated T1/ST2 signal transduction, using either transient overexpression of T1/ST2 or a cross-linking monoclonal antibody to activate cells. We demonstrate that T1/ST2 does not activate the transcription factor NF-?B when overexpressed in murine thymoma EL4 cells, or in the mast cell line P815 treated with the anti-T1/ST2 antibody. However, a chimera comprising the extracellular domain of the type 1 IL-1 receptor and the intracellular domain of T1/ST2 activates NF-?B both by overexpression and in response to IL-1. This artificial activation requires the IL1RAcP recruited via the extracellular portion (IL1R1) of the chimera. T1/ST2 is, however, able to activate the transcription factor activator protein-1 (AP-1), increase phosphorylation of c-Jun, and activate the MAP kinases c-Jun N-terminal kinase (JNK), p42/p44 and p38. Anti-T1/ST2 also induces the selective expression of IL-4 but not IFN-? in naive T cells. Importantly, this effect is blocked by prior treatment with the JNK inhibitor SP600125 confirming that JNK as a key effector in T1/ST2 signaling. The lack of effect on NF-?B when T1/ST2 is homodimerized identifies T1/ST2 as the first member of the IL-1 receptor superfamily so far studied that is apparently unable to activate NF-?B, consistent with evidence indicating the lack of a role for NF-?B in Th2 cell function.en
dc.format.extent344575 bytes
dc.format.extent49205en
dc.format.extent49211en
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.relation.ispartofseriesJournal of Biological Chemistryen
dc.relation.ispartofseries277en
dc.relation.ispartofseries51en
dc.rightsYen
dc.subjectClinical Medicineen
dc.titleCharacterization of signaling pathways activated by the interleukin 1 (IL-1) receptor homologue T1/ST2. A role for Jun N-terminal kinase in IL-4 inductionen
dc.typeJournal Articleen
dc.contributor.sponsorEnterprise Ireland
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/pfallon
dc.identifier.rssinternalid25376
dc.identifier.rssurihttp://dx.doi.org/10.1074/jbc.M209685200


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