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.
Malinin
N L
NL
Department of Membrane Research and Biophysics, The Weizmann Institute of Science, Rehovot, Israel.
Boldin
M P
MP
Kovalenko
A V
AV
Wallach
D
D
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D020930:MAP Kinase Kinase Kinases; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015398:Signal Transduction; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*; D000097782:NF-kappaB-Inducing Kinase
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D053200:Fas-Associated Death Domain Protein; D007375:Interleukin-1; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D000097782:NF-kappaB-Inducing Kinase; C505533:FADD protein, human; C506249:RIPK1 protein, human