Abstract
Signaling via the pre-T cell receptor (pre-TCR) regulates survival, proliferation, allelic exclusion and differentiation of thymocytes. The role played by the adapter protein Shc in T cells has remained controversial, and its role in pre-TCR signaling has not been addressed. We examined Shc function in thymic T cell development using two genetic approaches. Cre-loxP-mediated inducible expression in transgenic mice of a phosphorylation-defective mutant of Shc impaired signaling through the pre-TCR as well as subsequent proliferation and differentiation. Conditional deletion of the Shc locus in thymocytes also affected thymic maturation at the same pre-TCR developmental stage. Thus, both Shc expression and its tyrosine phosphorylation play an essential and nonredundant role in thymic T cell development.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Adaptor Proteins, Vesicular Transport*
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Animals
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Flow Cytometry
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Gene Expression Regulation / genetics
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Gene Expression Regulation / immunology
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Immunoblotting
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology
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Mice
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Mice, Knockout
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Mice, Transgenic
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Mutagenesis, Insertional
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Phosphorylation
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Proteins / genetics
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Proteins / immunology*
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Receptors, Antigen, T-Cell, alpha-beta
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Shc Signaling Adaptor Proteins
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Src Homology 2 Domain-Containing, Transforming Protein 1
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Membrane Glycoproteins
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Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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Shc Signaling Adaptor Proteins
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Shc1 protein, mouse
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Src Homology 2 Domain-Containing, Transforming Protein 1
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pre-T cell receptor alpha