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

Several members of the tumour-necrosis/nerve-growth factor (TNF/NGF) receptor family activate the transcription factor NF-kappaB through a common adaptor protein, Traf2 (refs 1-5), whereas the interleukin 1 type-I receptor activates NF-kappaB independently of Traf2 (ref. 4). We have now cloned a new protein kinase, NIK, which binds to Traf2 and stimulates ...
NF-kappaB activity. This kinase shares sequence similarity with several MAPKK kinases. Expression in cells of kinase-deficient NIK mutants fails to stimulate NF-kappaB 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-kappaB induction by interleukin-1. Our findings indicate that NIK participates in an NF-kappaB-inducing signalling cascade common to receptors of the TNF/NGF family and to the interleukin-1 type-I receptor.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Antigens, CD95, Carrier Proteins, Cell Line, Cloning, Molecular, Fas-Associated Death Domain Protein, Humans, Interleukin-1, MAP Kinase Kinase Kinases, Molecular Sequence Data, NF-kappa B, Protein Binding, Protein-Serine-Threonine Kinases, Proteins, Receptor-Interacting Protein Serine-Threonine Kinases, Saccharomyces cerevisiae, Signal Transduction, TNF Receptor-Associated Factor 1, TNF Receptor-Associated Factor 2, Transfection, Tumor Necrosis Factor-alpha
Nature
Date: Feb. 06, 1997
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