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

Li Zhang, Victoria Camerini, Timothy P. Bender, Kodi S. Ravichandran

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


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.

Original languageEnglish
Pages (from-to)749-755
Number of pages7
JournalNature immunology
Issue number8
StatePublished - Aug 2002


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