Abstract
Through its type 1 receptor (TNFR1), the cytokine TNF elicits an unusually wide range of biological responses, including inflammation, tumor necrosis, cell proliferation, differentiation, and apoptosis. We investigated how TNFR1 activates different effector functions; the protein kinase JNK, transcription factor NF-kappaB, and apoptosis. We found that the three responses are mediated through separate pathways. Recruitment of the signal transducer FADD to the TNFR1 complex mediates apoptosis but not NF-kappaB or JNK activation. Two other signal transducers, RIP and TRAF2, mediate both JNK and NF-kappaB activation. These two responses, however, diverge downstream to TRAF2. Most importantly, JNK activation is not involved in induction of apoptosis, while activation of NF-kappaB protects against TNF-induced apoptosis.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma / pathology
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Antigens, CD / physiology*
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Apoptosis / physiology*
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Arabidopsis Proteins*
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Breast Neoplasms / pathology
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Enzyme Activation
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Fatty Acid Desaturases / physiology
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Female
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HeLa Cells
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Humans
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JNK Mitogen-Activated Protein Kinases*
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MAP Kinase Kinase 4
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Mitogen-Activated Protein Kinase Kinases*
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NF-kappa B / physiology*
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Neoplasm Proteins / physiology
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Phosphorylation
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Plant Proteins / physiology
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Protein Kinases / physiology*
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Protein Processing, Post-Translational*
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Receptors, Tumor Necrosis Factor / physiology*
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Receptors, Tumor Necrosis Factor, Type I
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / physiology*
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Transfection
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / physiology
Substances
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Antigens, CD
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Arabidopsis Proteins
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NF-kappa B
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Neoplasm Proteins
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Plant Proteins
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Recombinant Fusion Proteins
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Tumor Necrosis Factor-alpha
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Fatty Acid Desaturases
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Fad7 protein, Arabidopsis
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Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 4
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Mitogen-Activated Protein Kinase Kinases