RasGRP is essential for mouse thymocyte differentiation and TCR signaling

Nancy A. Dower, Stacey L. Stang, Drell A. Bottorff, Julius Ebinu, Peter Dickie, Hanne L. Ostergaard, James C. Stone

Research output: Contribution to journalArticlepeer-review

359 Scopus citations


The Ras signaling pathway plays a critical role in thymopoiesis and T cell activation, but the mechanism of Ras regulation is controversial. At least one mode of Ras regulation in T cells involves the messenger diacylglycerol (DAG). RasGRP, a Ras activator with a DAG-binding CI domain, is expressed in T cells and thymocytes. Here we show that thymi of RasGRP-null mutant mice have approximately normal numbers of immature thymocytes but a marked deficiency of mature, single-positive (CD4+CD8- and CD4-CD8+) thymocytes. In Ras signaling and proliferation assays, mutant thymocytes showed a complete lack of response to DAG analogs or T cell receptor (TCR) stimulation by antibodies. Thus, TCR and DAG are linked through RasGRP to Ras signaling.

Original languageEnglish (US)
Pages (from-to)317-321
Number of pages5
JournalNature Immunology
Issue number4
StatePublished - Jan 1 2000
Externally publishedYes

ASJC Scopus subject areas

  • Immunology


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