Radons, Juergen and Gabler, Stefan and Wesche, Holger and Korherr, Christian and Hofmeister, Robert and Falk, Werner (2002) Identification of essential regions in the cytoplasmic tail of interleukin-1 receptor accessory protein critical for interleukin-1 signaling. JOURNAL OF BIOLOGICAL CHEMISTRY, 277 (19). pp. 16456-16463. ISSN 0021-9258
Full text not available from this repository. (Request a copy)Abstract
Interleukin (IL)-1 plays an important role in inflammation and regulation of immune responses. The activated IL-1 receptor complex, which consists of the IL-1 receptor type I and the IL-1 receptor accessory protein (IL-1RAcP), generates multiple cellular responses including NF-kappaB activation, IL-2 secretion, and IL-2 promoter activation. Reconstitution experiments in EL4D6/76 cells lacking IL-1RAcP expression and IL-1 responsiveness were used to analyze structure-function relationships of the IL-1RAcP cytoplasmic tail. Mutating a potential tyrosine kinase phosphorylation motif and various conserved amino acid (aa) residues had no effect on IL-1 responsiveness. Truncation analyses revealed that box 3 of the TIR domain was required for NF-kappaB activation, IL-2 production, and c-Jun N-terminal kinase (JNK) activation, whereas IL-2 promoter activation was only partially inhibited. Surprisingly, deletion of aa 527-534 resulted in almost complete loss of all IL-1 responsiveness. Replacement of these aa with alanyl residues did not reconstitute NF-kappaB activation, IL-2 production, or JNK activation but partly restored IL-2 promoter activation. Immunoprecipitation data revealed a strong correlation between MyD88 binding with NF-kappaB activation and IL-2 production but not with IL-2 promoter activation. Taken together, our data indicate that box 3 of IL-1RAcP is critical for IL-1-dependent NF-kappaB activation and stabilization of IL-2 mRNA via JNK, whereas aa 527-534 largely contribute to IL-2 promoter activation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; IL-1 RECEPTOR; MESSENGER-RNA; TRANSCRIPTION FACTOR; ADAPTER PROTEIN; KINASE PATHWAY; TAK1 MAPKKK; ACTIVATION; TRANSDUCTION; IRAK; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Oct 2021 09:14 |
| Last Modified: | 26 Oct 2021 09:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/40263 |
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