RasGRP is essential for mouse thymocyte differentiation and TCR signaling.
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 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.
Dower
N A
NA
Department of Pediatrics, University of Alberta, Edmonton Alberta, Canada, T6G 2H7.
Stang
S L
SL
Bottorff
D A
DA
Ebinu
J O
JO
Dickie
P
P
Ostergaard
H L
HL
Stone
J C
JC
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000276:immunology; D020662:Guanine Nucleotide Exchange Factors; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; C112278:Rasgrp1 protein, mouse; D011948:Receptors, Antigen, T-Cell