Nature Immunology
6, 881 - 888 (2005)
Published online: 31 July 2005; Corrected online: 14 August 2005 | doi:10.1038/ni1234
Notch promotes survival of pre−T cells at the  -selection checkpoint by regulating cellular metabolismMaria Ciofani
& Juan Carlos Zúñiga-Pflücker
Department of Immunology, University of Toronto, Sunnybrook and Women's Research Institute, Toronto, Ontario M4N 3M5, Canada.
Correspondence should be addressed to Juan Carlos Zúñiga-Pflücker jczp@swri.ca Notch signals are necessary for the functional outcomes of T cell receptor  -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 -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.*Note: In the version of this article initially published online, in the fourth sentence of the abstract, the term "Atk" was a misspelling; this should be "Akt." In the fourth sentence of the second paragraph of the introduction, the name of the second kinase mentioned, "PI(3)K-dependent kinase 1," was incorrect; this should read "phosphoinositide-dependent kinase 1." These errors have been corrected for the HTML and print versions of the article.
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