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.
Zhang
Li
L
Beirne B. Carter Center for Immunology Research and Department of Microbiology University of Virginia, Charlottesville, VA 22908, USA.
Camerini
Victoria
V
Bender
Timothy P
TP
Ravichandran
Kodi S
KS
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D015151:Immunoblotting; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D010766:Phosphorylation; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D008562:Membrane Glycoproteins; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D055765:Shc Signaling Adaptor Proteins; C528034:Shc1 protein, mouse; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C090377:pre-T cell receptor alpha