标题：Specific intercellular binding of the β-amyloid precursor protein to the presenilins induces intercellular signaling: Its significance for Alzheimer’s disease
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：25
页码：15055-15060
DOI：10.1073/pnas.95.25.15055
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Genetic evidence has implicated three proteins, the {beta}-amyloid precursor protein ({beta}-APP) and the two homologous presenilins (PS-1 and PS-2), in the etiology of Alzheimer's disease (AD). How these three proteins jointly contribute to AD, however, is not clear. Nor is any of their normal physiological functions known. Herein, we demonstrate, confirming a prediction made earlier, that {beta}-APP and either PS-1 or PS-2 act as a specific membrane-bound ligand binding intercellularly with either of its two membrane receptors. This results in a cell-cell adhesion, after which rapid transient increases in protein tyrosine kinase activity and protein tyrosine phosphorylation occur coordinately inside one or both of the two adherent cells. The spectrum of proteins modified by tyrosine phosphorylation differs depending on whether PS-1 or PS-2 is involved in the specific intercellular binding to {beta}-APP, which implies that PS-1 and PS-2 have distinct, rather than redundant, functions in normal physiology. The relevance of this intercellular interaction and signaling process to AD is discussed.
