title: Targeted Sos1 deletion reveals its critical role in early T-cell development.
abstract: 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 of sos1 to 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.
authors: National Cancer Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Robert L
authors: RL
authors: Kortum
authors: Connie L
authors: CL
authors: Sommers
authors: Clayton P
authors: CP
authors: Alexander
authors: John M
authors: JM
authors: Pinski
authors: Wenmei
authors: W
authors: Li
authors: Alex
authors: A
authors: Grinberg
authors: Jan
authors: J
authors: Lee
authors: Paul E
authors: PE
authors: Love
authors: Lawrence E
authors: LE
authors: Samelson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D005260:Female; D018390:Gene Targeting; D020662:Guanine Nucleotide Exchange Factors / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D020837:SOS1 Protein / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D020664:Son of Sevenless Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C112278:Rasgrp1 protein, mouse; D011948:Receptors, Antigen, T-Cell; D020837:SOS1 Protein; D020664:Son of Sevenless Proteins; C116864:Sos2 protein, mouse