期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2001
卷号：98
期号：8
页码：4461-4465
DOI：10.1073/pnas.071054198
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Mutant I1A cells, lacking IL-1 receptor-associated kinase (IRAK) mRNA and protein, have been used to study the involvement of IRAK in NF{kappa}B 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 NF{kappa}B and JNK activation, whereas the N-proximal undetermined domain is required for the activation of NF{kappa}B but not JNK. The phosphorylation and ubiquitination of IRAK deletion mutants correlate tightly with their ability to activate NF{kappa}B 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 NF{kappa}B and JNK activation diverge either at IRAK or at a point nearer to the receptor.
