Membrane-anchored metalloprotease MDC9 has an alpha-secretase activity responsible for processing the amyloid precursor protein - PubMed (original) (raw)

. 1999 Oct 15;343 Pt 2(Pt 2):371-5.

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Membrane-anchored metalloprotease MDC9 has an alpha-secretase activity responsible for processing the amyloid precursor protein

H Koike et al. Biochem J. 1999.

Abstract

MDC9, also known as meltrin gamma, is a membrane-anchored metalloprotease. MDC9 contains several distinct protein domains: a signal sequence followed by a prodomain and a domain showing sequence similarity to snake venom metalloproteases, a disintegrin-like domain, a cysteine-rich region, an epidermal-growth-factor-like repeat, a transmembrane domain and a cytoplasmic domain. Here we demonstrate that MDC9 expressed in COS cells is cleaved between the prodomain and the metalloprotease domain. Further, when MDC9 was co-expressed in COS cells with amyloid precursor protein (APP695) and treated with phorbol ester, APP695 was digested exclusively at the alpha-secretory site in MDC9-expressing cells. When an artificial alpha-secretory site mutant was also co-expressed with MDC9 and treated with phorbol ester, APP secreted by alpha-secretase was not increased in conditional medium. Inhibition of MDC9 by a hydroxamate-based metalloprotease inhibitor, SI-27, enhanced beta-secretase cleavage. These results suggest that MDC9 has an alpha-secretase-like activity and is activated by phorbol ester.

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References

    1. FEBS Lett. 1997 Jan 6;400(3):333-5 - PubMed
    1. J Biol Chem. 1997 Jan 3;272(1):556-62 - PubMed
    1. Nature. 1997 Feb 20;385(6618):729-33 - PubMed
    1. Nature. 1997 Feb 20;385(6618):733-6 - PubMed
    1. Dev Biol. 1997 Jun 15;186(2):155-64 - PubMed

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