Targeted Sos1 Deletion Reveals Its Critical Role in Early T-cell Development

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2011 Jul 13

PMID 21746917

Citations 47

Authors

Robert L Kortum

Connie L Sommers

Clayton P Alexander

John M Pinski

Wenmei Li

Alex Grinberg

Jan Lee

Paul E Love

Lawrence E Samelson

Affiliations

Soon will be listed here.

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.

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