Notch promotes survival of pre-T cells at the beta-selection checkpoint by regulating cellular metabolism.

Published

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.

Full Text

Duke Authors

Cited Authors

  • Ciofani, M; Zúñiga-Pflücker, JC

Published Date

  • September 2005

Published In

Volume / Issue

  • 6 / 9

Start / End Page

  • 881 - 888

PubMed ID

  • 16056227

Pubmed Central ID

  • 16056227

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/ni1234

Language

  • eng

Conference Location

  • United States