Tyrosine phosphorylation of I kappa B-alpha activates NF-kappa B without proteolytic degradation of I kappa B-alpha

Cell. 1996 Sep 6;86(5):787-98. doi: 10.1016/s0092-8674(00)80153-1.

Abstract

The transcription factor NF-kappa B regulates genes participating in immune and inflammatory responses. In T lymphocytes, NF-kappa B is sequestered in the cytosol by the inhibitor I kappa B-alpha and released after serine phosphorylation of I kappa B-alpha that regulates its ubiquitin-dependent degradation. We report an alternative mechanism of NF-kappa B activation. Stimulation of Jurkat T cells with the protein tyrosine phosphatase inhibitor and T cell activator pervanadate led to NF-kappa B activation through tyrosine phosphorylation but not degradation of I kappa B-alpha. Pervanadate-induced I kappa B-alpha phosphorylation and NF-kappa B activation required expression of the T cell tyrosine kinase p56ick. Reoxygenation of hypoxic cells appeared as a physiological effector of I kappa B-alpha tyrosine phosphorylation. Tyrosine phosphorylation of I kappa B-alpha represents a proteolysis-independent mechanism of NF-kappa B activation that directly couples NF-kappa B to cellular tyrosine kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Base Sequence
  • Calcimycin / pharmacology
  • Cell Hypoxia
  • DNA / metabolism
  • DNA-Binding Proteins / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Genistein
  • Humans
  • I-kappa B Proteins*
  • Ionophores / pharmacology
  • Isoflavones / pharmacology
  • Leukocyte Common Antigens / pharmacology
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Molecular Sequence Data
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / physiology*
  • Phosphorylation
  • Protein Binding
  • Protein Kinase C / antagonists & inhibitors
  • Protein Tyrosine Phosphatases / antagonists & inhibitors
  • Staurosporine
  • T-Lymphocytes
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcriptional Activation / physiology*
  • Tumor Cells, Cultured
  • Tyrosine / metabolism*
  • Vanadates / pharmacology
  • src-Family Kinases / antagonists & inhibitors
  • src-Family Kinases / physiology

Substances

  • Alkaloids
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • I-kappa B Proteins
  • Ionophores
  • Isoflavones
  • NF-kappa B
  • NFKBIA protein, human
  • pervanadate
  • NF-KappaB Inhibitor alpha
  • Calcimycin
  • Vanadates
  • Tyrosine
  • DNA
  • Genistein
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • src-Family Kinases
  • Protein Kinase C
  • Leukocyte Common Antigens
  • Protein Tyrosine Phosphatases
  • Staurosporine
  • Tetradecanoylphorbol Acetate