Cellular processing of the neurotrophin precursors of NT3 and BDNF by the mammalian proprotein convertases

Cellular processing of the neurotrophin precursors of NT3 and BDNF by the mammalian proprotein convertases
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DOI:
10.1016/0014-5793(95)01520-5
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发表时间:
1996-02-05
期刊:
影响因子:
3.5
通讯作者:
Murphy, RA
Murphy, RA
中科院分区:
生物学3区
文献类型:
--
作者:
Seidah, NG;Benjannet, S;Murphy, RA

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为了定义负责脑源性神经营养因子 (proBDNF) 和神经营养蛋白-3 (proNT3) 前体成熟的酶,我们分析了前蛋白转化酶弗林蛋白酶、PC1、PC2、PACE4、PC5 及其亚型 PC5/6-B 的生物合成和细胞内加工。在这些研究中,我们在 BSC40 或弗林蛋白酶活性缺陷的 LoVo 细胞中利用痘苗病毒表达系统,结果表明,在这两种细胞中,弗林蛋白酶以及较小程度的 PACE4 和 PC5/6-B 都能有效处理 proBDNF 和 proNT3。此外,Pie 还确定人类 proNT3 被硫酸化,这表明 proNT3 的加工发生在前体到达高尔基体网络之后。
In order to define the enzymes responsible for the maturation of the precursors of brain-derived neurotrophic factor (proBDNF) and neurotrophin-3 (proNT3), we have analysed their biosynthesis and intracellular processing by the proprotein convertases furin, PC1, PC2, PACE4, PC5 and its isoform PC5/6-B. In these studies, we utilized a vaccinia virus expression system in either BSC40 or the furin activity-deficient LoVo cells, Results demonstrated that in both cells furin and, to a lesser extent, PACE4 and PC5/6-B effectively process proBDNF and proNT3. Furthermore, pie have determined that human proNT3 is sulfated, suggesting that processing of proNT3 occurs following the arrival of the precursor to the Trans Golgi Network.