Signal transduction by activated mNotch: Importance of proteolytic processing and its regulation by the extracellular domain
Signal transduction by activated mNotch: Importance of proteolytic processing and its regulation by the extracellular domain
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DOI：
10.1073/pnas.93.4.1683
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发表时间：
1996-02-20
影响因子：
11.1
通讯作者：
Nye, JS
中科院分区：
文献类型：
--
作者：
Kopan, R;Schroeter, EH;Nye, JS
先前的研究表明Notch 1的胞内结构域必须易位到细胞核才能发挥其活性。在这项研究中，我们证明了mNotch 1突变蛋白，缺乏其胞外结构域，但保留其跨膜区成为蛋白水解处理的细胞内表面，因此，激活的细胞内结构域在细胞内位点的蛋白水解切割被蛋白酶抑制剂阻断，在用无活性变体转染的细胞中未观察到细胞内裂解，所述无活性变体包括细胞外lin-Notch-glp重复序列。总的来说，这里提出的研究支持mNotch 1蛋白水解加工和切割产物易位到细胞核的mNotch 1信号转导的模型。
Previous studies imply that the intracellular domain of Notch1 must translocate to the nucleus for its activity. In this study, we demonstrate that a mNotch 1 mutant protein that lacks its extracellular domain but retains its membrane-spanning region becomes proteolytically processed on its intracellular surface and, as a result, the activated intracellular domain (mNotchIC) is released and can move to the nucleus, Proteolytic cleavage at an intracellular site is blocked by protease inhibitors, Intracellular cleavage is not seen in cells transfected with an inactive variant, which includes the extracellular lin-Notch-glp repeats. Collectively, the studies presented here support the model that mNotch1 is proteolytically processed and the cleavage product is translocated to the nucleus for mNotch1 signal transduction.