Nature Immunology
3, 749 - 755 (2002)
Published online: 8 July 2002; | doi:10.1038/ni820
A nonredundant role for the adapter protein Shc in thymic T cell developmentLi Zhang1, 2, Victoria Camerini1, 3, Timothy P. Bender1, 2, 4
& Kodi S. Ravichandran1, 2, 41
Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908, USA. 2
Department of Microbiology University of Virginia, Charlottesville, VA 22908, USA. 3
Department of Pediatrics, University of Virginia, Charlottesville, VA 22908, USA. 4
T. P. B. and K. S. R. contributed equally to this work.
Correspondence should be addressed to Kodi S. Ravichandran ravi@virginia.eduSignaling 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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