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

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.

Pubmed ID: 12101399


  • Zhang L
  • Camerini V
  • Bender TP
  • Ravichandran KS


Nature immunology

Publication Data

August 29, 2002

Associated Grants

  • Agency: NCI NIH HHS, Id: CA85842
  • Agency: NIGMS NIH HHS, Id: GM-55761

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Animals
  • Flow Cytometry
  • Gene Expression Regulation
  • Immunoblotting
  • Membrane Glycoproteins
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Mutagenesis, Insertional
  • Phosphorylation
  • Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Shc Signaling Adaptor Proteins
  • Signal Transduction
  • T-Lymphocytes