RasGRP essential for mouse thymocyte differentiation and TCR signaling

被引：357

作者：

Dower, NA

Stang, SL

Bottorff, DA

Ebinu, JO

Dickie, P

Ostergaard, HL

Stone, JC ^{[1
]}

机构：

[1] Univ Alberta, Dept Biochem, Edmonton, AB T6G 2H7, Canada

[2] Univ Alberta, Dept Pediat, Edmonton, AB T6G 2H7, Canada

[3] Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB T6G 2H7, Canada

来源：

NATURE IMMUNOLOGY | 2000年 / 1卷 / 04期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1038/79766

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 Cl domain, is expressed inT 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.

引用

页码：317 / 321

页数：5

共 39 条

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