| First Author | Ciofani M | Year | 2005 |
| Journal | Nat Immunol | Volume | 6 |
| Issue | 9 | Pages | 881-8 |
| PubMed ID | 16056227 | Mgi Jnum | J:100457 |
| Mgi Id | MGI:3588591 | Doi | 10.1038/ni1234 |
| Citation | Ciofani M, et al. (2005) Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism. Nat Immunol 6(9):881-8 |
| abstractText | Notch signals are necessary for the functional outcomes of T cell receptor beta-selection, including differentiation, proliferation and rescue from apoptosis. The mechanism underlying this requirement for T cell development is unknown. Here we show that Notch receptor and Delta-like 1 ligand interactions promoted the survival of CD4(-)CD8(-) pre-T cells through the maintenance of cell size, glucose uptake and metabolism. Furthermore, the trophic effects of Notch signaling were mediated by the pathway of phosphatidylinositol-3-OH kinase and the kinase Akt, such that expression of active Atk overcame the requirement for Notch in beta-selection. Collectively, our results demonstrate involvement of Notch receptor-ligand interactions in the regulation of cellular metabolism, thus enabling the autonomous signaling capacity of the pre-T cell receptor complex. |
