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
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids / pharmacology
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Base Sequence
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Calcimycin / pharmacology
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Cell Hypoxia
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DNA / metabolism
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DNA-Binding Proteins / metabolism*
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Enzyme Inhibitors / pharmacology
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Genistein
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Humans
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I-kappa B Proteins*
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Ionophores / pharmacology
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Isoflavones / pharmacology
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Leukocyte Common Antigens / pharmacology
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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Molecular Sequence Data
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NF-KappaB Inhibitor alpha
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NF-kappa B / physiology*
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Phosphorylation
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Protein Binding
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Protein Kinase C / antagonists & inhibitors
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Protein Tyrosine Phosphatases / antagonists & inhibitors
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Staurosporine
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T-Lymphocytes
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Tetradecanoylphorbol Acetate / pharmacology
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Transcriptional Activation / physiology*
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Tumor Cells, Cultured
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Tyrosine / metabolism*
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Vanadates / pharmacology
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src-Family Kinases / antagonists & inhibitors
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src-Family Kinases / physiology
Substances
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Alkaloids
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DNA-Binding Proteins
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Enzyme Inhibitors
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I-kappa B Proteins
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Ionophores
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Isoflavones
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NF-kappa B
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NFKBIA protein, human
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pervanadate
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NF-KappaB Inhibitor alpha
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Calcimycin
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Vanadates
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Tyrosine
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DNA
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Genistein
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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src-Family Kinases
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Protein Kinase C
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Leukocyte Common Antigens
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Protein Tyrosine Phosphatases
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Staurosporine
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Tetradecanoylphorbol Acetate