Abstract
IFN-alpha inhibits B lymphocyte development, and the nuclear protein Daxx has been reported to be essential for this biological activity. We show in this study that IFN-alpha inhibits the clonal proliferation of B lymphocyte progenitors in response to IL-7 in wild-type, but not in tyk2-deficient, mice. In addition, the IFN-alpha-induced up-regulation and nuclear translocation of Daxx are completely abrogated in the absence of tyk2. Therefore, tyk2 is directly involved in IFN-alpha signaling for the induction and translocation of Daxx, which may result in B lymphocyte growth arrest and/or apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus / genetics
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Active Transport, Cell Nucleus / immunology
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Animals
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B-Lymphocytes / cytology*
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B-Lymphocytes / enzymology*
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B-Lymphocytes / immunology
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Bone Marrow Cells / cytology
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Bone Marrow Cells / enzymology
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Bone Marrow Cells / immunology
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Carrier Proteins / biosynthesis
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Carrier Proteins / metabolism*
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Carrier Proteins / physiology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Line
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Cells, Cultured
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Co-Repressor Proteins
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Coculture Techniques
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Growth Inhibitors / physiology*
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / enzymology
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Hematopoietic Stem Cells / immunology
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Immunosuppressive Agents / pharmacology*
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Interferon-alpha / physiology*
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Interleukin-7 / antagonists & inhibitors
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Interleukin-7 / physiology
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Intracellular Signaling Peptides and Proteins*
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Mice
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Mice, Knockout
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Molecular Chaperones
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / metabolism*
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Nuclear Proteins / physiology
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Protein-Tyrosine Kinases / deficiency
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / physiology*
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Proteins / genetics
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Proteins / physiology*
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TYK2 Kinase
Substances
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Carrier Proteins
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Co-Repressor Proteins
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Daxx protein, mouse
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Growth Inhibitors
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Immunosuppressive Agents
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Interferon-alpha
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Interleukin-7
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Intracellular Signaling Peptides and Proteins
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Molecular Chaperones
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Nuclear Proteins
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Proteins
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Protein-Tyrosine Kinases
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TYK2 Kinase
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Tyk2 protein, mouse