IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation

Science. 1997 Oct 31;278(5339):860-6. doi: 10.1126/science.278.5339.860.

Abstract

Activation of the transcription factor nuclear factor kappa B (NF-kappaB) is controlled by sequential phosphorylation, ubiquitination, and degradation of its inhibitory subunit IkappaB. A large multiprotein complex, the IkappaB kinase (IKK) signalsome, was purified from HeLa cells and found to contain a cytokine-inducible IkappaB kinase activity that phosphorylates IkappaB-alpha and IkappaB-beta. Two components of the IKK signalsome, IKK-1 and IKK-2, were identified as closely related protein serine kinases containing leucine zipper and helix-loop-helix protein interaction motifs. Mutant versions of IKK-2 had pronounced effects on RelA nuclear translocation and NF-kappaB-dependent reporter activity, consistent with a critical role for the IKK kinases in the NF-kappaB signaling pathway.

MeSH terms

  • Cell Cycle Proteins*
  • Cloning, Molecular
  • Dual Specificity Phosphatase 1
  • Enzyme Activation
  • HeLa Cells
  • Helix-Loop-Helix Motifs
  • Humans
  • I-kappa B Kinase
  • Immediate-Early Proteins / metabolism
  • Leucine Zippers
  • Molecular Sequence Data
  • NF-kappa B / metabolism*
  • Phosphoprotein Phosphatases*
  • Phosphorylation
  • Protein Phosphatase 1
  • Protein Tyrosine Phosphatases / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • Sequence Homology, Amino Acid
  • Substrate Specificity

Substances

  • Cell Cycle Proteins
  • Immediate-Early Proteins
  • NF-kappa B
  • Protein-Serine-Threonine Kinases
  • CHUK protein, human
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1
  • DUSP1 protein, human
  • Dual Specificity Phosphatase 1
  • Protein Tyrosine Phosphatases