Abstract
The biological actions of tumor necrosis factor alpha (TNF-alpha) are mediated by two cell surface receptors, TNFR-1 and TNFR-2. These receptors do not display protein tyrosine kinase activity. Nevertheless, an early TNF-induced activation of specific tyrosine kinases has been reported as an important cue to the cellular response to this cytokine. Here we present evidence that TNF-alpha induces the activation of the cytoplasmic Janus tyrosine kinases Jak1 and Tyk2 in both human healthy peripheral and lymphoma B cells. This event was accompanied by the recruitment of a specific set of latent cytosolic transcription factors, Stat3 and Stat5b. Furthermore, Jak1 coprecipitated with TNFR-1 after TNF-alpha treatment. These data suggest that at least in human B cells this cytokine can exert its biological effects through the Jak-Stat signaling pathway and that such signals are initiated through an interaction between TNFR-1 and Jak 1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / metabolism*
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Apoptosis / drug effects
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B-Lymphocytes / drug effects
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B-Lymphocytes / enzymology*
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B-Lymphocytes / ultrastructure
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Cell Survival / drug effects
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Cells, Cultured
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DNA-Binding Proteins / metabolism*
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Enzyme Activation
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Humans
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Janus Kinase 1
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Lymphoma, B-Cell / enzymology*
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Microscopy, Fluorescence
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Milk Proteins*
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Phosphorylation
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Protein-Tyrosine Kinases / metabolism*
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Receptors, Tumor Necrosis Factor / metabolism*
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Receptors, Tumor Necrosis Factor, Type I
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STAT3 Transcription Factor
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STAT5 Transcription Factor
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Signal Transduction
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Trans-Activators / metabolism*
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / pharmacology*
Substances
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Antigens, CD
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DNA-Binding Proteins
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Milk Proteins
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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STAT3 Transcription Factor
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STAT3 protein, human
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STAT5 Transcription Factor
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STAT5B protein, human
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Trans-Activators
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Tumor Necrosis Factor-alpha
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Protein-Tyrosine Kinases
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JAK1 protein, human
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Janus Kinase 1