Abstract
The Syk/ZAP-70 family of protein tyrosine kinases is indispensable for normal lymphoid development. Syk is necessary for the development of B cells and epithelial gammadelta T cells, whereas ZAP-70 is essential for the normal development of T cells and TCR signaling. In this study, we show that although development of the alphabeta lineage was arrested in the thymus, CD3-positive T cells, primarily of the gammadelta lineage, were present in the lymph nodes of mice lacking ZAP-70. Moreover, in the absence of ZAP-70, dendritic epidermal T cells were fewer in number and of abnormal morphology, and intestinal intraepithelial lymphocytes, normally containing a large proportion of gammadelta T cells, were markedly reduced. These data suggest that gammadelta T cells show a variable dependence upon ZAP-70 for their development. Biochemical analyses of thymocytes revealed a lack of basal zeta-chain tyrosine phosphorylation. However, several other substrates were inducibly tyrosine phosphorylated following TCR stimulation. Thus, TCR-mediated signaling in ZAP-70-deficient thymocytes is only partially impaired. These studies suggest that Syk compensates only partially for the loss of ZAP-70, and that there is an absolute requirement of ZAP-70 for alphabeta T cells and epithelial gammadelta T cells, but not for some gammadelta T cells in peripheral lymphoid tissues.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Lineage
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Clonal Deletion*
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Dendritic Cells / immunology
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Dendritic Cells / pathology
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Enzyme Precursors / physiology
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Epidermis / immunology
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Epidermis / pathology
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Female
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Immunologic Deficiency Syndromes / immunology
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Immunologic Deficiency Syndromes / pathology
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Intestine, Small / immunology
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Intestine, Small / pathology
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Intracellular Signaling Peptides and Proteins
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Lymph Nodes / immunology
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Lymph Nodes / pathology
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Lymphocyte Count
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Lymphoid Tissue / immunology
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Lymphoid Tissue / pathology*
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Male
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Membrane Proteins / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Phosphorylation
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Protein Processing, Post-Translational*
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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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Receptors, Antigen, T-Cell / metabolism*
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Receptors, Antigen, T-Cell, alpha-beta / immunology*
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Receptors, Antigen, T-Cell, gamma-delta / immunology*
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Signal Transduction / physiology*
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Spleen / immunology
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Spleen / pathology
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Syk Kinase
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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Thymus Gland / immunology
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Thymus Gland / physiology
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ZAP-70 Protein-Tyrosine Kinase
Substances
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Enzyme Precursors
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Receptors, Antigen, T-Cell
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Antigen, T-Cell, gamma-delta
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antigen T cell receptor, zeta chain
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Protein-Tyrosine Kinases
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Syk Kinase
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Syk protein, mouse
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ZAP-70 Protein-Tyrosine Kinase
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Zap70 protein, mouse