Abstract
Viral infection or double-stranded (ds) RNA induce interferons (IFN) and other cytokines. Transcription factors mediating IFN induction are known, but the signaling pathways that regulate them are less clear. We now describe two such pathways. The first pathway leading to NF-kappaB depends on the dsRNA-responsive protein kinase (PKR), which in turn activates IKB kinase (IKK) through the IKKbeta subunit. The second viral-and dsRNA-responsive pathway is PKR independent and involves Jun kinase (JNK) activation leading to stimulation of AP-1. Both IKKbeta and JNK2 are essential for efficient induction of type I IFN and other cytokines in response to viral infection or dsRNA. This study establishes a general role for these kinases in activation of innate immune responses.
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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3T3 Cells
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Animals
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Cell Line, Transformed
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Enzyme Activation
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Gene Expression Regulation
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Humans
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I-kappa B Kinase
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Interferon-alpha / genetics
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Interferon-beta / genetics
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JNK Mitogen-Activated Protein Kinases
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Mice
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Mice, Knockout
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Mitogen-Activated Protein Kinase 9
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Mitogen-Activated Protein Kinases / metabolism
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Promoter Regions, Genetic
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Protein Kinases / genetics
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Protein Kinases / immunology*
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / immunology*
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Protein Serine-Threonine Kinases / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Vesicular stomatitis Indiana virus / immunology*
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eIF-2 Kinase / genetics
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eIF-2 Kinase / metabolism
Substances
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Interferon-alpha
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Recombinant Fusion Proteins
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Interferon-beta
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Protein Kinases
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Mitogen-Activated Protein Kinase 9
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Protein Serine-Threonine Kinases
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eIF-2 Kinase
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CHUK protein, human
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Chuk protein, mouse
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I-kappa B Kinase
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IKBKB protein, human
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IKBKE protein, human
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Ikbkb protein, mouse
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Ikbke protein, mouse
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases