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 RIS Download
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 | Src Homology 2 Domain-Containing, Transforming Protein 1 | T-Lymphocytes