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 journalArticle

345 Citations (Scopus)

Abstract

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
Volume1
Issue number4
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

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Diglycerides
Thymocytes
T-Cell Antigen Receptor
T-Lymphocytes
Thymus Gland
Antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

Dower, N. A., Stang, S. L., Bottorff, D. A., Ebinu, J., Dickie, P., Ostergaard, H. L., & Stone, J. C. (2000). RasGRP is essential for mouse thymocyte differentiation and TCR signaling. Nature Immunology, 1(4), 317-321. https://doi.org/10.1038/79766

RasGRP is essential for mouse thymocyte differentiation and TCR signaling. / Dower, Nancy A.; Stang, Stacey L.; Bottorff, Drell A.; Ebinu, Julius; Dickie, Peter; Ostergaard, Hanne L.; Stone, James C.

In: Nature Immunology, Vol. 1, No. 4, 01.01.2000, p. 317-321.

Research output: Contribution to journalArticle

Dower, NA, Stang, SL, Bottorff, DA, Ebinu, J, Dickie, P, Ostergaard, HL & Stone, JC 2000, 'RasGRP is essential for mouse thymocyte differentiation and TCR signaling', Nature Immunology, vol. 1, no. 4, pp. 317-321. https://doi.org/10.1038/79766
Dower NA, Stang SL, Bottorff DA, Ebinu J, Dickie P, Ostergaard HL et al. RasGRP is essential for mouse thymocyte differentiation and TCR signaling. Nature Immunology. 2000 Jan 1;1(4):317-321. https://doi.org/10.1038/79766
Dower, Nancy A. ; Stang, Stacey L. ; Bottorff, Drell A. ; Ebinu, Julius ; Dickie, Peter ; Ostergaard, Hanne L. ; Stone, James C. / RasGRP is essential for mouse thymocyte differentiation and TCR signaling. In: Nature Immunology. 2000 ; Vol. 1, No. 4. pp. 317-321.
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