Abstract
Mutant I1A cells, lacking IL-1 receptor-associated kinase (IRAK) mRNA and protein, have been used to study the involvement of IRAK in NFκB and c-Jun N-terminal kinase (JNK) activation. A series of IRAK deletion constructs were expressed in I1A cells, which were then tested for their ability to respond to IL-1. Both the N-terminal death domain and the C-terminal region of IRAK are required for IL-1-induced NFκB and JNK activation, whereas the N-proximal undetermined domain is required for the activation of NFκB but not JNK. The phosphorylation and ubiquitination of IRAK deletion mutants correlate tightly with their ability to activate NFκB in response to IL-1, but IRAK can mediate IL-1-induced JNK activation without being phosphorylated. These studies reveal that the IL-1-induced signaling pathways leading to NFκB and JNK activation diverge either at IRAK or at a point nearer to the receptor.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 10:37 a.m.) |
Deposited | 3 years, 4 months ago (April 12, 2022, 4:24 p.m.) |
Indexed | 1 week, 1 day ago (Aug. 20, 2025, 8:37 a.m.) |
Issued | 24 years, 4 months ago (April 3, 2001) |
Published | 24 years, 4 months ago (April 3, 2001) |
Published Online | 24 years, 4 months ago (April 3, 2001) |
Published Print | 24 years, 4 months ago (April 10, 2001) |
@article{Li_2001, title={IL-1-induced NFκB and c-Jun N-terminal kinase (JNK) activation diverge at IL-1 receptor-associated kinase (IRAK)}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.071054198}, DOI={10.1073/pnas.071054198}, number={8}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Li, Xiaoxia and Commane, Mairead and Jiang, Zhengfan and Stark, George R.}, year={2001}, month=apr, pages={4461–4465} }