Title |
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*
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Published in |
Journal of Biological Chemistry, October 2002
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DOI | 10.1074/jbc.m209685200 |
Pubmed ID | |
Authors |
Elizabeth K. Brint, Katherine A. Fitzgerald, Philip Smith, Anthony J. Coyle, Jose-Carlos Gutierrez-Ramos, Padraic G. Fallon, Luke A.J. O'Neill |
Abstract |
T1/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-kappaB 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-kappaB 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-gamma 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-kappaB 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-kappaB, consistent with evidence indicating the lack of a role for NF-kappaB in Th2 cell function. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 2% |
Unknown | 48 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 16 | 33% |
Student > Ph. D. Student | 12 | 24% |
Student > Bachelor | 2 | 4% |
Student > Doctoral Student | 2 | 4% |
Other | 2 | 4% |
Other | 6 | 12% |
Unknown | 9 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 20 | 41% |
Biochemistry, Genetics and Molecular Biology | 6 | 12% |
Medicine and Dentistry | 6 | 12% |
Neuroscience | 5 | 10% |
Immunology and Microbiology | 3 | 6% |
Other | 0 | 0% |
Unknown | 9 | 18% |