| First Author | Zha Y | Year | 2006 |
| Journal | Nat Immunol | Volume | 7 |
| Issue | 11 | Pages | 1166-73 |
| PubMed ID | 17028589 | Mgi Jnum | J:113566 |
| Mgi Id | MGI:3686962 | Doi | 10.1038/ni1394 |
| Citation | Zha Y, et al. (2006) T cell anergy is reversed by active Ras and is regulated by diacylglycerol kinase-alpha. Nat Immunol 7(11):1166-73 |
| abstractText | T cell anergy has been correlated with defective signaling by the GTPase Ras, but causal and mechanistic data linking defective Ras activity with T cell anergy are lacking. Here we used adenoviral transduction to genetically manipulate nonproliferating T cells and show that active Ras restored interleukin 2 production and mitogen-activated protein kinase signaling in T cells that were made anergic in vitro or in vivo. Diacylglycerol kinases (DGKs), which negatively regulate Ras activity, were upregulated in anergic T cells, and a DGK inhibitor restored interleukin 2 production in anergic T cells. Both anergy and DGK-alpha overexpression were associated with defective translocation of the Ras guanine nucleotide-exchange factor RasGRP1 to the plasma membrane. Our data support a causal function for excess DGK activity and defective Ras signaling in T cell anergy. |
