α-Secretase Activity of the Disintegrin Metalloprotease ADAM 10: Influences of Domain Structure

: Disintegrin metalloproteases from different organisms form the ADAM (adisintegrin and metalloprotease) family. All members display a common domain organization and possess four potential functions: proteolysis, cell adhesion, cell fusion, and cell signaling. Members of the ADAM family are responsi...

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Veröffentlicht in:Annals of the New York Academy of Sciences 2000-01, Vol.920 (1), p.215-222
Hauptverfasser: FAHRENHOLZ, FALK, GILBERT, SANDRA, KOJRO, ELZBIETA, LAMMICH, SVEN, POSTINA, ROLF
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container_title Annals of the New York Academy of Sciences
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creator FAHRENHOLZ, FALK
GILBERT, SANDRA
KOJRO, ELZBIETA
LAMMICH, SVEN
POSTINA, ROLF
description : Disintegrin metalloproteases from different organisms form the ADAM (adisintegrin and metalloprotease) family. All members display a common domain organization and possess four potential functions: proteolysis, cell adhesion, cell fusion, and cell signaling. Members of the ADAM family are responsible for the proteolytic cleavage of transmembrane proteins and release of their extracellular domain. The proteolytic process is referred to as ectodomain shedding, which is activated by phorbol esters and inhibited by hydroxamic acid‐based inhibitors. We have shown that the disintegrin metalloprotease ADAM 10 has both constitutive and regulated α‐secretase activity. Expression of a dominant negative mutant of ADAM 10 in HEK cells decreases the secretion of APPsα. In order to investigate the influence of distinct protein domains of ADAM 10 on α‐secretase activity, several deletion mutants of ADAM 10 were constructed. Our findings demonstrate that the deletion of the disintegrin domain results in a mutant ADAM 10 with remaining α‐secretase activity, whereas the deletion of the prodomain destroys the proteolytic activity of ADAM 10.
doi_str_mv 10.1111/j.1749-6632.2000.tb06925.x
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subjects ADAM Proteins
ADAM10 Protein
Amino Acid Sequence
Amyloid beta-Protein Precursor - chemistry
Amyloid beta-Protein Precursor - genetics
Amyloid beta-Protein Precursor - metabolism
Amyloid Precursor Protein Secretases
Animals
Aspartic Acid Endopeptidases
Disintegrins - metabolism
Endopeptidases - metabolism
Humans
Membrane Proteins - genetics
Membrane Proteins - metabolism
Metalloendopeptidases - genetics
Metalloendopeptidases - metabolism
Molecular Sequence Data
Protease Inhibitors - pharmacology
Protein Processing, Post-Translational
Recombinant Proteins - metabolism
title α-Secretase Activity of the Disintegrin Metalloprotease ADAM 10: Influences of Domain Structure
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