Processing of the Notch ligand delta by the metalloprotease kuzbanian
Processing of the Notch ligand delta by the metalloprotease kuzbanian
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DOI：
10.1126/science.283.5398.91
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发表时间：
1999-01-01
期刊：
影响因子：
56.9
通讯作者：
Artavanis-Tsakonas, S
中科院分区：
文献类型：
--
作者：
Qi, HL;Rand, MD;Artavanis-Tsakonas, S
Notch 表面受体的信号传导控制着广泛组织中的细胞命运决定。这种信号传导是由Notch蛋白与迄今为止被认为是邻近细胞上表达的跨膜配体的相互作用触发的。生化和遗传分析表明，配体 Delta 在表面裂解，释放出能够与 Notch 结合并充当 Notch 活性激动剂的细胞外片段。此加工过程需要 ADAM 解整合素金属蛋白酶 Kuzbanian。这些观察结果提出了体内Notch信号传导受Notch配体的可溶形式调节的可能性。
Signaling by the Notch surface receptor controls cell fate determination in a broad spectrum of tissues. This signaling is triggered by the interaction of the Notch protein with what, so far, have been thought to be transmembrane ligands expressed on adjacent cells. Here biochemical and genetic analyses show that the ligand Delta is cleaved on the surface, releasing an extracellular fragment capable of binding to Notch and acting as an agonist of Notch activity. The ADAM disintegrin metalloprotease Kuzbanian is required for this processing event. These observations raise the possibility that Notch signaling in vivo is modulated by soluble forms of the Notch ligands.