| pmid | 10094049 | ||||||
|---|---|---|---|---|---|---|---|
| title | The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. | ||||||
| authors |
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| journal | Nature | ||||||
| year | 1999 | ||||||
| full_text_available | false | ||||||
| doi | 10.1038/18465 |
The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway.
Authors: Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K Journal: Nature (1999) DOI: 10.1038/18465
- Nature. 1999 Mar 18;398(6724):252-6. doi: 10.1038/18465.
The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway.
Ninomiya-Tsuji J(1), Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K.
Author information: (1)Department of Molecular Biology, Graduate School of Science, Nagoya University, and CREST, Japan Science and Technology Corporation.
Interleukin-1 (IL-1) is a proinflammatory cytokine that has several effects in the inflammation process. When it binds to its cell-surface receptor, IL-1 initiates a signalling cascade that leads to activation of the transcription factor NF-kappaB and is relayed through the protein TRAF6 and a succession of kinase enzymes, including NF-kappaB-inducing kinase (NIK) and I kappaB kinases (IKKs). However, the molecular mechanism by which NIK is activated is not understood. Here we show that the MAPKK kinase TAK1 acts upstream of NIK in the IL-1-activated signalling pathway and that TAK1 associates with TRAF6 during IL-1 signalling. Stimulation of TAK1 causes activation of NF-kappaB, which is blocked by dominant-negative mutants of NIK, and an inactive TAK1 mutant prevents activation of NF-kappaB that is mediated by IL-1 but not by NIK. Activated TAK1 phosphorylates NIK, which stimulates IKK-alpha activity. Our results indicate that TAK1 links TRAF6 to the NIK-IKK cascade in the IL-1 signalling pathway.
DOI: 10.1038/18465 PMID: 10094049 [Indexed for MEDLINE]