AMYLOID PRECURSOR PROTEIN SECRETION AND BETA-A4 AMYLOID GENERATION ARE NOT MUTUALLY EXCLUSIVE
AMYLOID PRECURSOR PROTEIN SECRETION AND BETA-A4 AMYLOID GENERATION ARE NOT MUTUALLY EXCLUSIVE
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DOI：
10.1016/0014-5793(94)00671-7
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发表时间：
1994-08-01
期刊：
影响因子：
3.5
通讯作者：
TURNER, J
中科院分区：
文献类型：
--
作者：
DYRKS, T;MONNING, U;TURNER, J
调节淀粉样前体蛋白 (APP) 生成 β A4 的细胞因素尚不清楚。已发现蛋白激酶 C (PKC) 引起的蛋白质磷酸化会影响 APP 的加工和代谢。在本报告中，我们表明，在人神经母细胞瘤细胞系 SY5Y 中，PKC 激活不会改变全长 APP 生成 β A4，而刺激非淀粉样蛋白生成分泌片段 (APPsec) 和 β A4 C 末端片段 (p3) 的产生。此外，PKC 激活会刺激 APP 膜插入 C 端 100 个残基 (SPA4CT) 生成 β A4。因此，尝试将 APP 加工从淀粉样蛋白生成、β A4 生成转移到非淀粉样蛋白生成、分泌途径，必须解决这两种途径和/或导致 APP 在 β A4 结构域 C 末端裂解的过程的性质和调节。这里报告的数据表明这些机制是细胞类型特异性的。
The cellular factors regulating the generation of beta A4 from the amyloid precursor protein (APP) are unknown. Protein phosphorylation by protein kinase C (PKC) has been found to influence the processing and metabolism of APP. In this report, we show that in the human neuroblastoma cell line SY5Y, beta A4 generation from full-length APP is not changed by PKC activation whereas production of the non-amyloidogenic secretory fragment (APPsec) and of the C-terminal fragment of beta A4 (p3) are stimulated. In addition, beta A4 generation from the membrane inserted C-terminal 100 residues (SPA4CT) of APP is stimulated by PKC activation. Accordingly attempts to divert APP processing from the amyloidogenic, beta A4-generating, to the non-amyloidogenic, secretory, pathway, have to address the nature and regulation of the two pathways and/or of the process leading to the cleavage of APP at the C-terminus of the beta A4 domain. The data reported here suggest that these mechanisms are cell-type specific.