A secreted form of human ADAM9 has an α-secretase activity for APP

被引：82

作者：

Hotoda, N

Koike, H

Sasagawa, N

Ishiura, S

机构：

[1] Univ Tokyo, Dept Life Sci, Grad Sch Arts & Sci, Meguro Ku, Tokyo 1538902, Japan

[2] Meiji Pharmaceut Univ, Dept Biochem, Tokyo 2048588, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2002年 / 293卷 / 02期

关键词：

disintegrin metalloprotease; splicing form; amyloid precursor protein; alpha-secretase; proteolysis;

D O I：

10.1016/S0006-291X(02)00302-9

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：

ADAM9 (MDC9, meltrin gamma) is a member of the ADAM family of metalloproteases, which play important roles in cell-cell fusion. intracellular signaling, and other cellular functions. Here we cloned a novel form of human ADAM9, designated hADAM9s (s for short), which lacks the carboxyl-terminus. Human ADAM9s was found to be secreted from transfected COS cells. RT-PCR analysis demonstrated that the mRNA for hADAM9s is expressed in human brain, liver, heart. kidney, lung, and trachea. When hADAM9s was co-expressed in COS cells with APP and treated with phorbol ester. the APP was digested exclusively at the alpha-secretory site. These results suggest that hADAM9s has an alpha-secretase-like activity for APP. Non-amyloidgenic cleavage of APP may occur at the plasma membrane. Our new results support a new therapeutic strategy to decrease in the AP content by directly activating ADAM9 in the extracellular space. (C) 2002 Elsevier Science (USA). All rights reserved.

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页码：800 / 805

页数：6

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