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PMID: 21746917 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Targeted Sos1 deletion reveals its critical role in early T-cell development.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 108 ·No. 30 ·2011-07-26 ·Pages 12407-12

Kortum RL, Sommers CL, Alexander CP, Pinski JM, Li W, Grinberg A, Lee J, Love PE, Samelson LE

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.

MeSH Terms
Animals Cell Differentiation/immunology Cell Proliferation Female Gene Targeting Guanine Nucleotide Exchange Factors/immunology Male Mice Mice, Knockout Models, Immunological Receptors, Antigen, T-Cell/metabolism SOS1 Protein/deficiency,genetics,immunology Signal Transduction/immunology Son of Sevenless Proteins/immunology T-Lymphocytes/cytology,immunology
Chemicals
Guanine Nucleotide Exchange Factors Rasgrp1 protein, mouse Receptors, Antigen, T-Cell SOS1 Protein Son of Sevenless Proteins Sos2 protein, mouse
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Kortum Robert L
National Cancer Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Sommers Connie L
Alexander Clayton P
Pinski John M
Li Wenmei
Grinberg Alex
Lee Jan
Love Paul E
Samelson Lawrence E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1104295108
Published
2011-07-26
Epub
2011-00-11
Pages
12407-12
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC3145744
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1073/pnas.1104295108 PMC Full Text View journal details
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