Abstract
The c-Jun NH2-terminal kinase (JNK) signaling pathway has been implicated in the immune response that is mediated by the activation and differentiation of CD4 helper T (TH) cells into TH1 and TH2 effector cells. JNK activity observed in wild-type activated TH cells was severely reduced in TH cells from Jnk1-/- mice. The Jnk1-/- T cells hyperproliferated, exhibited decreased activation-induced cell death, and preferentially differentiated to TH2 cells. The enhanced production of TH2 cytokines by Jnk1-/- cells was associated with increased nuclear accumulation of the transcription factor NFATc. Thus, the JNK1 signaling pathway plays a key role in T cell receptor-initiated TH cell proliferation, apoptosis, and differentiation.
Publication types
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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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Animals
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Apoptosis
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Differentiation
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Cell Division
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DNA-Binding Proteins / metabolism
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Female
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Gene Targeting
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Hemocyanins / immunology
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Interferon-gamma / biosynthesis
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Interleukins / biosynthesis
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JNK Mitogen-Activated Protein Kinases
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Lymphocyte Activation*
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Male
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinases*
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NFATC Transcription Factors
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Nuclear Proteins*
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Signal Transduction
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
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Th1 Cells / cytology
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Th1 Cells / immunology
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Th2 Cells / cytology
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Th2 Cells / immunology
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Transcription Factors / metabolism
Substances
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DNA-Binding Proteins
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Interleukins
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NFATC Transcription Factors
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Nuclear Proteins
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Transcription Factors
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Interferon-gamma
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Hemocyanins
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Calcium-Calmodulin-Dependent Protein Kinases
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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keyhole-limpet hemocyanin