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PMID:11017103
| Citation |
Dower, NA, Stang, SL, Bottorff, DA, Ebinu, JO, Dickie, P, Ostergaard, HL and Stone, JC (2000) RasGRP is essential for mouse thymocyte differentiation and TCR signaling. Nat. Immunol. 1:317-21 |
|---|---|
| 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 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. |
| Links |
PubMed Online version:10.1038/79766 |
| Keywords |
Animals; Cell Differentiation/immunology; DNA-Binding Proteins/genetics; DNA-Binding Proteins/immunology; Gene Deletion; Gene Expression Regulation/immunology; Guanine Nucleotide Exchange Factors; Mice; Receptors, Antigen, T-Cell/genetics; Receptors, Antigen, T-Cell/immunology; Signal Transduction/immunology; T-Lymphocytes/cytology; T-Lymphocytes/immunology |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
involved_in |
GO:0033089: positive regulation of T cell differentiation in thymus |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0090630: activation of GTPase activity |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
| GO:0033089: positive regulation of T cell differentiation in thymus |
ECO:0000315: |
P |
Fig 2; inhibition of mouse RasGRP1 led to impaired T-cell differentiation |
complete | ||||
| GO:0090630: activation of GTPase activity |
ECO:0000315: |
P |
Fig 4; RasGRP inactivation in mutants led to no Ras activation |
complete | ||||
See also
References
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