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

Nature. 1997 Feb 6;385(6616):540-4. doi: 10.1038/385540a0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Carrier Proteins / metabolism
  • Cell Line
  • Cloning, Molecular
  • Fas-Associated Death Domain Protein
  • Humans
  • Interleukin-1 / physiology*
  • MAP Kinase Kinase Kinases
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Protein Binding
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Proteins / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Saccharomyces cerevisiae / genetics
  • Signal Transduction
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • Transfection
  • Tumor Necrosis Factor-alpha / physiology*
  • fas Receptor / physiology*


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • Interleukin-1
  • NF-kappa B
  • Proteins
  • TNF Receptor-Associated Factor 1
  • TNF Receptor-Associated Factor 2
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Protein Serine-Threonine Kinases
  • RIPK1 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • MAP Kinase Kinase Kinases
  • NF-kappa B kinase

Associated data

  • GENBANK/Y10256