Correlating notch signaling with thymocyte maturation.
The Notch receptor and its ligands are involved in many developmental processes. They are highly expressed in the thymus and have been implicated in the CD4 versus CD8 lineage decision. We identified the constitutively active intracellular fragment of murine Notch-1 as capable of rendering thymomas resistant to glucocorticoid-induced apoptosis. This effect was confirmed in other T cell lines and in CD4+ CD8+ DP thymocytes. Activation of the Notch signaling pathway also upregulated a number of other markers that, like steroid resistance, correlate with DP maturation into both the CD4 and CD8 lineages. These results suggest that Notch signaling is critically involved in the maturation of DP thymocytes into both CD4+ and CD8+ SP thymocytes.
Deftos
M L
ML
Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA.
He
Y W
YW
Ojala
E W
EW
Bevan
M J
MJ
D000818:Animals; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D029721:Drosophila Proteins; D004351:Drug Resistance; D005938:Glucocorticoids / Q000494:pharmacology; D019476:Insect Proteins / Q000235:genetics; D007424:Intracellular Fluid; D019891:Leukopoiesis; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D010449:Peptide Mapping; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051881:Receptor, Notch1; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D013950:Thymus Gland; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
C086679:DX protein, Drosophila; D029721:Drosophila Proteins; D005938:Glucocorticoids; D019476:Insect Proteins; D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D051881:Receptor, Notch1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011956:Receptors, Cell Surface; D014157:Transcription Factors