Abstract
The linker molecule LAT is a substrate of the tyrosine kinases activated following TCR engagement. Phosphorylated LAT binds many critical signaling molecules. The central role of this molecule in TCR-mediated signaling has been demonstrated by experiments in a LAT-deficient cell line. To probe the role of LAT in T cell development, the LAT gene was disrupted by targeting. LAT-deficient mice appeared healthy. Flow cytometric analysis revealed normal B cell populations but the absence of any mature peripheral T cells. Intrathymic development was blocked within the CD4- CD8- stage. No gross abnormality of NK or platelet function was observed. LAT is thus critical to both T cell activation and development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Animals
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Carrier Proteins / genetics
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Carrier Proteins / immunology
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Carrier Proteins / physiology*
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Cell Differentiation / immunology
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Killer Cells, Natural / cytology
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Killer Cells, Natural / immunology
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Membrane Proteins / genetics
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Membrane Proteins / immunology
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Membrane Proteins / physiology*
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Mice
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Mice, Inbred Strains
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Mice, Knockout
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Phosphoproteins / genetics
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Phosphoproteins / immunology
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Phosphoproteins / physiology*
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / physiology
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Receptors, Antigen, T-Cell, gamma-delta / genetics
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Receptors, Antigen, T-Cell, gamma-delta / metabolism
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Lat protein, mouse
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Membrane Proteins
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Phosphoproteins
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Receptors, Antigen, T-Cell
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Receptors, Antigen, T-Cell, gamma-delta