Targeted Sos1 deletion reveals its critical role in early T-cell development
Copyright policy )Targeted Sos1 deletion reveals its critical role in early T-cell development
Activation of the small G protein Ras is required for thymocyte differentiation. In thymocytes, Ras is activated by the Ras guanine exchange factors (RasGEFs) Sos1, Sos2, and RasGRP1. We report the development of a floxed allele ofsos1to assess the role of Sos1 during thymocyte development. Sos1 was required for pre–T-cell receptor (pre-TCR)– but not TCR-stimulated developmental signals. Sos1 deletion led to a partial block at the DN-to-DP transition. Sos1-deficient thymocytes showed reduced pre-TCR–stimulated proliferation, differentiation, and ERK phosphorylation. In contrast, TCR-stimulated positive selection, and negative selection under strong stimulatory conditions, remained intact in Sos1-deficient mice. Comparison of RasGEF expression at different developmental stages showed that relative to Sos2 and RasGRP1, Sos1 is most abundant in DN thymocytes, but least abundant in DP thymocytes. These data reveal that Sos1 is uniquely positioned to affect signal transduction early in thymocyte development.
- National Institutes of Health United States
- National Institute of Health Pakistan
- National Cancer Institute Malaysia
- National Institute of Child Health and Human Development United States
- Ministry of Health Malaysia
Male, Mice, Knockout, T-Lymphocytes, Models, Immunological, Receptors, Antigen, T-Cell, Cell Differentiation, Mice, Son of Sevenless Proteins, Gene Targeting, Animals, Guanine Nucleotide Exchange Factors, Female, SOS1 Protein, Cell Proliferation, Signal Transduction
Male, Mice, Knockout, T-Lymphocytes, Models, Immunological, Receptors, Antigen, T-Cell, Cell Differentiation, Mice, Son of Sevenless Proteins, Gene Targeting, Animals, Guanine Nucleotide Exchange Factors, Female, SOS1 Protein, Cell Proliferation, Signal Transduction
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