MAP3K-related kinase involved in NF-kappa B induction by TNF, CD95 and IL-1
MAP3K-related kinase involved in NF-kappa B induction by TNF, CD95 and IL-1
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DOI：
10.1038/385540a0
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发表时间：
1997-02-06
期刊：
影响因子：
64.8
通讯作者：
Wallach, D
中科院分区：
文献类型：
--
作者：
Malinin, NL;Boldin, MP;Wallach, D
肿瘤坏死/神经生长因子（TNF/NGF）受体家族的几个成员通过共同的衔接蛋白Traf 2激活转录因子NF-κ B（参考文献1-5），而白细胞介素1 I型受体独立于Traf 2激活NF-κ B（参考文献4）。我们现在已经克隆了一种新的蛋白激酶NIK，它与Traf 2结合并刺激NF-κ B活性。该激酶与几种MAPKK激酶具有序列相似性。激酶缺陷型NIK突变体在细胞中的表达不能刺激NF-κ B，并阻断TNF、两种TNF受体或受体CD 95（Fas/Apo-1）以及TRADD、RIP和MORT 1/FADD（与这些受体结合的衔接蛋白）对其的诱导。它还阻断了白细胞介素-1对NF-κ B B的诱导。我们的研究结果表明，NIK参与了一个NF-κ B诱导信号级联共同的受体的TNF/NGF家族和白细胞介素-1 I型受体。
Several members of the tumour-necrosis/nerve-growth factor (TNF/NGF) receptor family activate the transcription factor NF-kappa B through a common adaptor protein, Traf2 (refs 1-5), whereas the interleukin 1 type-I receptor activates NF-kappa B independently of Traf2 (ref. 4). We have now cloned a new protein kinase, NIK, which binds to Traf2 and stimulates NF-kappa B activity. This kinase shares sequence similarity with several MAPKK kinases. Expression in cells of kinase-deficient NIK mutants fails to stimulate NF-kappa B 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-kappa B induction by interleukin-l. Our findings indicate that NIK participates in an NF-kappa B-inducing signalling cascade common to receptors of the TNF/NGF family and to the interleukin-1 type-I receptor.