A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB

Nature. 1997 Aug 7;388(6642):548-54. doi: 10.1038/41493.

Abstract

Nuclear transcription factors of the NF-kappaB/Rel family are inhibited by IkappaB proteins, which inactivate NF-kappaB by trapping it in the cell cytoplasm. Phosphorylation of IkappaBs marks them out for destruction, thereby relieving their inhibitory effect on NF-kappaB. A cytokine-activated protein kinase complex, IKK (for IkappaB kinase), has now been purified that phosphorylates IkappaBs on the sites that trigger their degradation. A component of IKK was molecularly cloned and identified as a serine kinase. IKK turns out to be the long-sought-after protein kinase that mediates the critical regulatory step in NF-kappaB activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Cloning, Molecular
  • Enzyme Activation
  • HeLa Cells
  • Humans
  • I-kappa B Kinase
  • Inflammation Mediators / metabolism
  • Kinetics
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / isolation & purification
  • Protein-Serine-Threonine Kinases / metabolism*
  • Substrate Specificity
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Inflammation Mediators
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Protein-Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • Phosphoprotein Phosphatases

Associated data

  • GENBANK/AF009225