Abstract
Activation of Janus tyrosine kinases (Jak) and Signal transducers and activators of transcription (Stat) after ligation of major histocompatibility complex class I (MHC-I) was explored in Jurkat T cells. Cross-linking of MHC-I mediated tyrosine phosphorylation of Tyk2, but not Jak1, Jak2, and Jak3. In addition, the transcription factor Stat-3 was tyrosine phosphorylated in the cytoplasm and subsequently translocated to the cell nucleus. Data obtained by electrophoretic mobility shift assay suggested that the activated Stat-3 protein associates with the human serum-inducible element (hSIE) DNA-probe derived from the interferon-gamma activated site (GAS) in the c-fos promoter, a common DNA sequence for Stat protein binding. An association between hSIE and Stat-3 after MHC-I ligation was directly demonstrated by precipitating Stat-3 from nuclear extracts with biotinylated hSIE probe and avidin-coupled agarose. To investigate the function of the activated Stat-3, Jurkat T cells were transiently transfected with a Stat-3 isoform lacking the transactivating domain. This dominant-negative acting Stat-3 isoform significantly inhibited apoptosis induced by ligation of MHC-I. In conclusion, our data suggest the involvement of the Jak/Stat signal pathway in MHC-I-induced signal transduction in T cells.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal / immunology
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Apoptosis / physiology*
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Avidin / immunology
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Biological Transport
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Biotin / immunology
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Cell Nucleus / enzymology
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Cytoplasm / enzymology
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DNA-Binding Proteins / physiology*
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Enzyme Activation
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Gene Expression Regulation, Leukemic
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Genes, fos
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HLA Antigens / immunology*
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Humans
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Interferon-gamma / physiology
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Jurkat Cells / enzymology
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Jurkat Cells / immunology*
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Lymphocyte Activation / physiology*
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Macromolecular Substances
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Neoplasm Proteins / physiology
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Phosphorylation
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Protein Processing, Post-Translational / physiology*
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Protein-Tyrosine Kinases*
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Proteins / physiology*
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Receptor-CD3 Complex, Antigen, T-Cell / immunology*
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Recombinant Fusion Proteins / physiology
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STAT3 Transcription Factor
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Signal Transduction / physiology*
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T-Lymphocytes / enzymology
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T-Lymphocytes / immunology*
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TYK2 Kinase
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Trans-Activators / physiology*
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Transfection
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beta 2-Microglobulin / immunology
Substances
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Antibodies, Monoclonal
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DNA-Binding Proteins
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HLA Antigens
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Macromolecular Substances
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Neoplasm Proteins
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Proteins
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Receptor-CD3 Complex, Antigen, T-Cell
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Recombinant Fusion Proteins
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STAT3 Transcription Factor
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STAT3 protein, human
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Trans-Activators
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beta 2-Microglobulin
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Avidin
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Biotin
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Interferon-gamma
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Protein-Tyrosine Kinases
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TYK2 Kinase
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TYK2 protein, human