Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Cell Differentiation / immunology
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Cell Line
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Cell Size
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Cell Survival
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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Glucose / metabolism
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Glycolysis
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Intracellular Signaling Peptides and Proteins
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Ligands
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Membrane Proteins / metabolism
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Mice
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Mice, Knockout
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Phosphatidylinositol 3-Kinases / metabolism
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Receptor, Notch1
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Receptors, Antigen, T-Cell, alpha-beta / metabolism*
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Receptors, Cell Surface / metabolism*
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Signal Transduction
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T-Lymphocytes / cytology*
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T-Lymphocytes / metabolism*
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Transcription Factors / metabolism*
Substances
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DNA-Binding Proteins
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Intracellular Signaling Peptides and Proteins
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Ligands
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Membrane Proteins
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Notch1 protein, mouse
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Rag2 protein, mouse
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Receptor, Notch1
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Cell Surface
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Transcription Factors
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V(D)J recombination activating protein 2
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delta protein
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Glucose