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    Nat Immunol. 2002 Aug;3(8):749-55. Epub 2002 Jul 8.

    A nonredundant role for the adapter protein Shc in thymic T cell development.

    Zhang L, Camerini V, Bender TP, Ravichandran KS.

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    Beirne B. Carter Center for Immunology Research and Department of Microbiology University of Virginia, Charlottesville, VA 22908, USA.

    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.

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    PMID:
    12101399
    [PubMed - indexed for MEDLINE]

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