Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism.
Journal Article (Journal Article)
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.
- Ciofani, M; Zúñiga-Pflücker, JC
- September 2005
Volume / Issue
- 6 / 9
Start / End Page
- 881 - 888
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)
- United States