Nature Immunology
1, 317 - 321 (2000)
doi:10.1038/79766
RasGRP is essential for mouse thymocyte differentiation and TCR signaling
Nancy A. Dower1, Stacey L. Stang2, Drell A. Bottorff2, Julius O. Ebinu2, Peter Dickie3, Hanne L. Ostergaard3
& James C. Stone21
Department of Pediatrics, University of Alberta,
Edmonton Alberta, Canada, T6G 2H7. 2
Department of Biochemistry, University of Alberta,
Edmonton Alberta, Canada, T6G 2H7. 3
Department of Medical Microbiology and Immunology,
University of Alberta, Edmonton Alberta, Canada,
T6G 2H7.
Correspondence should be addressed to James C. Stone jim.stone@ualberta.caThe 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 C1 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.
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