The Notch Ligands Dll4 and Jagged1 Have Opposing Effects on Angiogenesis
The Notch Ligands Dll4 and Jagged1 Have Opposing Effects on Angiogenesis
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DOI：
10.1016/j.cell.2009.03.025
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发表时间：
2009-06-12
期刊：
影响因子：
64.5
通讯作者：
Adams, Ralf H.
中科院分区：
文献类型：
--
作者：
Benedito, Rui;Roca, Cristina;Adams, Ralf H.
Notch途径是一种高度保守的信号系统，控制着多种生长、分化和模式化过程。在生长的血管中，内皮尖端细胞的发芽受到Notch信号传导的抑制，Notch信号传导通过Notch受体与其配体Delta样4（Dll 4）的结合而被激活。在这里，我们发现Notch配体Jagged 1是一种有效的促血管生成调节剂，在小鼠中拮抗表达边缘家族糖基转移酶的细胞中的Dll 4-Notch信号传导。在Notch糖基化后，Dll 4-Notch信号传导增强，而Jaggedl具有弱信号传导能力并与Dll 4竞争。我们的研究结果表明，具有不同空间表达模式和相反功能作用的两种Notch配体之间的平衡调节血管生成，这种机制也可能适用于其他Notch控制的生物过程。
The Notch pathway is a highly conserved signaling system that controls a diversity of growth, differentiation, and patterning processes. In growing blood vessels, sprouting of endothelial tip cells is inhibited by Notch signaling, which is activated by binding of the Notch receptor to its ligand Delta-like 4 (Dll4). Here, we show that the Notch ligand Jagged1 is a potent proangiogenic regulator in mice that antagonizes Dll4-Notch signaling in cells expressing Fringe family glycosyltransferases. Upon glycosylation of Notch, Dll4-Notch signaling is enhanced, whereas Jagged1 has weak signaling capacity and competes with Dll4. Our findings establish that the equilibrium between two Notch ligands with distinct spatial expression patterns and opposing functional roles regulates angiogenesis, a mechanism that might also apply to other Notch-controlled biological processes.