期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 68, 期 6, 页码 655-667出版社
WILEY-LISS
DOI: 10.1002/jnr.10263
关键词
Delta; jagged; activation; inhibition; Notch signaling
资金
- NIDCD NIH HHS [R01-DC04061] Funding Source: Medline
- NINDS NIH HHS [R01-NS31885-09] Funding Source: Medline
Signaling induced through interactions between DSL (Delta, serrate, LAG-2) ligand-signaling cells and Notch-responding cells influences the developmental fate of a wide variety of invertebrate and vertebrate cell types. Consistently with a requirement for direct cell-cell interactions, secreted DSL ligands expressed in flies do not appear to activate Notch signaling but rather produce phenotypes reminiscent of losses in Notch signaling. In contrast, secreted DSL ligands expressed in Caenorhabditis elegans or supplied to mammalian cells in culture produce effects indicative of Notch activation. In fact, engineered secreted DSL ligands have been used to study Notch signaling in neurogenesis, gliogenesis, hematopoeisis, neurite morphogenesis and ligand-induced nuclear translocation of the Notch intracellular domain. Using a recombinant, secreted form of the DSL ligand Delta1, we found that anti body-induced oligomerization (termed clustering) was required for this soluble ligand to bind specifically to Notch1-expressing cells, undergo internalization, and activate downstream signaling. Interestingly, clustering with either limiting or excess antibody led to ligand binding in the absence of Notch signaling, indicating that ligand binding is necessary but not sufficient for activation of Notch signaling. Moreover, such antibody clustering conditions blocked Notch1 signaling induced by membrane-bound DSL ligands. We propose that multimerization influences whether ligand binding to Notch results in activation or inhibition of downstream signaling and suggest that differences in ligand presentation might account for why secreted forms of DSL ligands have been reported to function as agonists and antagonists of Notch signal transduction. (C) 2002 Wiley-Liss, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据