Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation

Science. 1995 Mar 10;267(5203):1485-8. doi: 10.1126/science.7878466.

Abstract

I kappa B-alpha inhibits transcription factor NF-kappa B by retaining it in the cytoplasm. Various stimuli, typically those associated with stress or pathogens, rapidly inactivate I kappa B-alpha. This liberates NF-kappa B to translocate to the nucleus and initiate transcription of genes important for the defense of the organism. Activation of NF-kappa B correlates with phosphorylation of I kappa B-alpha and requires the proteolysis of this inhibitor. When either serine-32 or serine-36 of I kappa B-alpha was mutated, the protein did not undergo signal-induced phosphorylation or degradation, and NF-kappa B could not be activated. These results suggest that phosphorylation at one or both of these residues is critical for activation of NF-kappa B.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • I-kappa B Proteins*
  • Ionomycin / pharmacology
  • Mice
  • Molecular Sequence Data
  • Mutation
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Phosphorylation
  • Point Mutation
  • Signal Transduction
  • T-Lymphocytes
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcriptional Activation
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • DNA-Binding Proteins
  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Ionomycin
  • Tetradecanoylphorbol Acetate