Fine-tuning Notch1 activation by endocytosis and glycosylation

被引:19
作者
Koch, U [1 ]
Yuan, JS [1 ]
Harper, JA [1 ]
Guidos, CJ [1 ]
机构
[1] Univ Toronto, Hosp Sick Children, Res Inst, Dept Immunol,Program Dev Biol, Toronto, ON M5G 1X8, Canada
基金
加拿大健康研究院;
关键词
T/B lineage commitment; lymphocyte progenitors; endocytosis; glycosyltransferases;
D O I
10.1016/S1044-5323(03)00006-X
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Recent studies have shown that disruption of Notchl signaling in lymphocyte progenitors (LP) inhibits T cell development and promotes B cell development in the thymus. Conversely, inappropriate activation of Notchl in LP inhibits B cell development and causes ectopic T cell development in the bone marrow. These observations imply that Notchl activation must be spatially regulated to ensure that LP generate B cells in the bone marrow and T cells in the thymus. However, Notch ligands are expressed in both tissues. Studies in flies and worms have revealed that Notch activation is extremely sensitive to small changes in the amount of receptor or ligand expressed, and defined multiple mechanisms that limit Notch activation to discrete cells at specific times during development. Here, we describe how some of these mechanisms might regulate Notch activity in LP during the T/B lineage decision. (C) 2003 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:99 / 106
页数:8
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