A novel substrate for analyzing Alzheimer's disease γ-secretase

被引：46

作者：

Lichtenthaler, SF

Multhaup, G

Masters, CL

Beyreuther, K

机构：

[1] Heidelberg Univ, ZMBH, Ctr Mol Biol Heidelberg, D-69120 Heidelberg, Germany

[2] Univ Melbourne, Parkville, Vic 3052, Australia

来源：

FEBS LETTERS | 1999年 / 453卷 / 03期

关键词：

signal peptidase; gamma-secretase; Alzheimer's disease; amyloid precursor protein; protein transport;

D O I：

10.1016/S0014-5793(99)00730-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Proteolytic processing of Alzheimer's disease amyloid precursor protein (APP) by beta-secretase leads to A4CT (C99), which is further cleaved by the as yet unknown protease called gamma-secretase, To study the enzymatic properties of gamma-secretase independently of beta-secretase, A4CT together with an N-terminal signal peptide (SPA4CT) may be expressed in eukaryotic cells. However, in all existing SPA4CT proteins the signal peptide is not correctly cleaved upon membrane insertion. Here, we report the generation of a mutated SPA4CT protein that is correctly cleaved by signal peptidase and, thus, identical to the APP-derived A4CT. This novel SPA4CT protein is processed by gamma-secretase in the same manner as APP-derived A4CT and might be valuable for the generation of transgenic animals shelving amyloid pathology, (C) 1999 Federation of European Biochemical Societies.

引用

页码：288 / 292

页数：5

共 33 条

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