Activated Ras signals differentiation and expansion of CD4+8+ hymocytes

Wojciech Swat, Yoichi Shinkai, Hwei Ling Cheng, Laurie Davidson, Frederick W. Alt

Research output: Contribution to journalArticle

118 Scopus citations


We describe a novel approach to assay the ability of particular gene products to signal transitions in lymphocyte differention in vivo. The method involves transfection of test expression constructs into RAG-1-deficient embryonic stem cells, which are subsequently assayed by the RAG-2-deficient blastocyst complementation approach. We have used this method to demonstrate that expression of activated Ras in CD4-8- (double negative, DN) prothymocytes in vivo induces their differentiation into small CD4+8+ (double postitive, DP) cortical thymocytes with accompanying expansion to normal thymocyte numbers. However, activated Ras expression in DP cells does not cause proliferation or maturation to CD4+8+ or CD4-8+ (single positive) thymocytes. Therefore, signaling through Ras is sufficient for promoting differentiation of DN to DP cells, but further differentiation requires the activity of additional signaling pathways.

Original languageEnglish
Pages (from-to)4683-4687
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
StatePublished - May 14 1996
Externally publishedYes

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