蛋白质O-岩藻糖基转移酶1是Notch信号通路的重要组成部分。
Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways.
作者信息
Shi Shaolin, Stanley Pamela
机构信息
Department of Cell Biology, Albert Einstein College Medicine, New York, NY 10461, USA.
出版信息
Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5234-9. doi: 10.1073/pnas.0831126100. Epub 2003 Apr 15.
Notch receptor signaling regulates cell growth and differentiation, and core components of Notch signaling pathways are conserved from Drosophila to humans. Fringe glycosyltransferases are crucial modulators of Notch signaling that act on epidermal growth factor (EGF)-like repeats in the Notch receptor extracellular domain. The substrate of Fringe is EGF-O-fucose and the transfer of fucose to Notch by protein O-fucosyltransferase 1 is necessary for Fringe to function. O-fucose also occurs on Cripto and on Notch ligands. Here we show that mouse embryos lacking protein O-fucosyltransferase 1 die at midgestation with severe defects in somitogenesis, vasculogenesis, cardiogenesis, and neurogenesis. The phenotype is similar to that of embryos lacking downstream effectors of all Notch signaling pathways such as presenilins or RBP-J kappa, and is different from Cripto, Notch receptor, Notch ligand, or Fringe null phenotypes. Protein O-fucosyltransferase 1 is therefore an essential core member of Notch signaling pathways in mammals.
Notch受体信号传导调节细胞生长和分化，并且Notch信号通路的核心成分从果蝇到人类都是保守的。边缘糖基转移酶是Notch信号传导的关键调节因子，作用于Notch受体胞外域中的表皮生长因子（EGF）样重复序列。边缘糖基转移酶的底物是EGF - O - 岩藻糖，蛋白质O - 岩藻糖基转移酶1将岩藻糖转移至Notch是边缘糖基转移酶发挥功能所必需的。O - 岩藻糖也存在于Cripto和Notch配体上。在此我们表明，缺乏蛋白质O - 岩藻糖基转移酶1的小鼠胚胎在妊娠中期死亡，在体节发生、血管发生、心脏发生和神经发生方面存在严重缺陷。该表型类似于缺乏所有Notch信号通路的下游效应器（如早老素或RBP - Jκ）的胚胎，并且不同于Cripto、Notch受体、Notch配体或边缘糖基转移酶缺失的表型。因此，蛋白质O - 岩藻糖基转移酶1是哺乳动物Notch信号通路的一个必需的核心成员。
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