Tyrosine phosphorylation of I kappa B-alpha activates NF-kappa B without proteolytic degradation of I kappa B-alpha.
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.
Imbert
V
V
Inserm Unité 364 Faculté de Médecine Pasteur, Nice, France.
Rupec
R A
RA
Livolsi
A
A
Pahl
H L
HL
Traenckner
E B
EB
Mueller-Dieckmann
C
C
Farahifar
D
D
Rossi
B
B
Auberger
P
P
Baeuerle
P A
PA
Peyron
J F
JF
D000470:Alkaloids / Q000494:pharmacology; D001483:Base Sequence; D000001:Calcimycin / Q000494:pharmacology; D015687:Cell Hypoxia; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein; D006801:Humans; D020672:I-kappa B Proteins; D007476:Ionophores / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000494:pharmacology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D019311:Staurosporine; D013601:T-Lymphocytes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015533:Transcriptional Activation / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
D000470:Alkaloids; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; D007476:Ionophores; D007529:Isoflavones; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C076715:pervanadate; D000072000:NF-KappaB Inhibitor alpha; D000001:Calcimycin; D014638:Vanadates; D014443:Tyrosine; D004247:DNA; D019833:Genistein; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases; D011493:Protein Kinase C; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate