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MAP3K-related kinase involved in NF-KB induction by TNF, CD95 and IL-1

Nature volume 385, pages 540–544 (1997)Cite this article

Abstract

Several members of the tumour-necrosis/nerve-growth factor (TNF/NGF) receptor family activate the transcription factor NF-KB through a common adaptor protein, Traf2 (refs 1–5), whereas the interleukin 1 type-I receptor activates NF-KB independently of Traf2 (ref. 4). We have now cloned a new protein kinase, NIK, which binds to Traf2 and stimulates NF-KB activity. This kinase shares sequence similarity with several MAPKK kinases. Expression in cells of kinase-deficient NIK mutants fails to stimulate NF-KB and blocks its induction by TNF, by either of the two TNF receptors or by the receptor CD95 (Fas/Apo-1), and by TRADD, RIP and MORT1/FADD, which are adaptor proteins that bind to these receptors. It also blocked NF-KB induction by interleukin-1. Our findings indicate that NIK participates in an NF-KB-inducing signalling cascade common to receptors of the TNF/NGF family and to the interleukin-1 type-I receptor.

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Authors and Affiliations

  1. Department of Membrane Research and Biophysics, The Weizmann Institue of Science, 76100, Rehovot, Israel

    Nikolai L. Malinin, Mark P. Boldin, Andrei V. Kovalenko & David Wallach

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  1. Nikolai L. Malinin
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  2. Mark P. Boldin
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  3. Andrei V. Kovalenko
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  4. David Wallach
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Malinin, N., Boldin, M., Kovalenko, A. et al. MAP3K-related kinase involved in NF-KB induction by TNF, CD95 and IL-1. Nature 385, 540–544 (1997). https://doi.org/10.1038/385540a0

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