Amyloid precursor protein secretion and βA4 amyloid generation are not mutually exclusive

FEBS Letters

Dyrks, Thomas¹  Mönning, Ursula²  Beyreuther, Konrad²  Turner, Jonathan¹ 

[1] Research Laboratories of Schering AG, D-13342 Berlin, Germany;Center for Molecular Biology, University of Heidelberg, Heidelberg, Germany

关键词: APP;    A4CT;    βA4;    Porcessing;    SY5Y;    Alzheimer's disease;   

DOI  :  10.1016/0014-5793(94)00671-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The cellular factors regulating the generation of βA4 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, βA4 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 βA4 (p3) are stimulated. In addition, βA4 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, βA4-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 βA4 domain. The data reported here suggest that these mechanisms are cell-type specific.

【 授权许可】

Unknown