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 |
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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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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.</description><identifier>ISSN: 0077-8923</identifier><identifier>EISSN: 1749-6632</identifier><identifier>DOI: 10.1111/j.1749-6632.2000.tb06925.x</identifier><identifier>PMID: 11193153</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>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</subject><ispartof>Annals of the New York Academy of Sciences, 2000-01, Vol.920 (1), p.215-222</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4095-ebca0c148f2c2173372bbe517ab93c081a8bf637f009b1f737def48c54efea0a3</citedby><cites>FETCH-LOGICAL-c4095-ebca0c148f2c2173372bbe517ab93c081a8bf637f009b1f737def48c54efea0a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1749-6632.2000.tb06925.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1749-6632.2000.tb06925.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11193153$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>FAHRENHOLZ, FALK</creatorcontrib><creatorcontrib>GILBERT, SANDRA</creatorcontrib><creatorcontrib>KOJRO, ELZBIETA</creatorcontrib><creatorcontrib>LAMMICH, SVEN</creatorcontrib><creatorcontrib>POSTINA, ROLF</creatorcontrib><title>α-Secretase Activity of the Disintegrin Metalloprotease ADAM 10: Influences of Domain Structure</title><title>Annals of the New York Academy of Sciences</title><addtitle>Ann N Y Acad Sci</addtitle><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.</description><subject>ADAM Proteins</subject><subject>ADAM10 Protein</subject><subject>Amino Acid Sequence</subject><subject>Amyloid beta-Protein Precursor - chemistry</subject><subject>Amyloid beta-Protein Precursor - genetics</subject><subject>Amyloid beta-Protein Precursor - metabolism</subject><subject>Amyloid Precursor Protein Secretases</subject><subject>Animals</subject><subject>Aspartic Acid Endopeptidases</subject><subject>Disintegrins - metabolism</subject><subject>Endopeptidases - metabolism</subject><subject>Humans</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Metalloendopeptidases - genetics</subject><subject>Metalloendopeptidases - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Protein Processing, Post-Translational</subject><subject>Recombinant Proteins - metabolism</subject><issn>0077-8923</issn><issn>1749-6632</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkN1O2zAYQC20CUq3V5giLnaXzH-JE26mio6fqbChDqFdGcd8BndpwmwH2sfai-yZ5tAKrucbX_h8x_ZB6IDgjMT1aZERwau0KBjNKMY4CzUuKppnqx00ejl6g0YYC5GWFWV7aN_7BcaEllzsor1oqRjJ2Qjd_P2TzkE7CMpDMtHBPtqwTjqThHtIptbbNsCds21yHpGm6R5cF-CZnU7OE4IPk7PWND20GvwwNu2WKtLz4Hodegfv0FujGg_vt_sYXR1_-XF0ms6-nZwdTWap5rjKU6i1wprw0lBNiWBM0LqGnAhVV0zjkqiyNgUTBuOqJkYwcQuGlzrnYEBhxcbo48YbH_i7Bx_k0noNTaNa6HovBc0pK3gRwcMNqF3nvQMjH5xdKreWBMuhr1zIIaIcIsqhr9z2las4_GF7S18v4fZ1dBs0Ap83wJNtYP0fannxczKnUTFG6cZgfYDVi0G5X7KI387l9cWJ_CqOL2f8-6Xk7B9MOJs6</recordid><startdate>20000101</startdate><enddate>20000101</enddate><creator>FAHRENHOLZ, FALK</creator><creator>GILBERT, SANDRA</creator><creator>KOJRO, ELZBIETA</creator><creator>LAMMICH, SVEN</creator><creator>POSTINA, ROLF</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20000101</creationdate><title>α-Secretase Activity of the Disintegrin Metalloprotease ADAM 10: Influences of Domain Structure</title><author>FAHRENHOLZ, FALK ; GILBERT, SANDRA ; KOJRO, ELZBIETA ; LAMMICH, SVEN ; POSTINA, ROLF</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4095-ebca0c148f2c2173372bbe517ab93c081a8bf637f009b1f737def48c54efea0a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>ADAM Proteins</topic><topic>ADAM10 Protein</topic><topic>Amino Acid Sequence</topic><topic>Amyloid beta-Protein Precursor - chemistry</topic><topic>Amyloid beta-Protein Precursor - genetics</topic><topic>Amyloid beta-Protein Precursor - metabolism</topic><topic>Amyloid Precursor Protein Secretases</topic><topic>Animals</topic><topic>Aspartic Acid Endopeptidases</topic><topic>Disintegrins - metabolism</topic><topic>Endopeptidases - metabolism</topic><topic>Humans</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Metalloendopeptidases - genetics</topic><topic>Metalloendopeptidases - metabolism</topic><topic>Molecular Sequence Data</topic><topic>Protease Inhibitors - pharmacology</topic><topic>Protein Processing, Post-Translational</topic><topic>Recombinant Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>FAHRENHOLZ, FALK</creatorcontrib><creatorcontrib>GILBERT, SANDRA</creatorcontrib><creatorcontrib>KOJRO, ELZBIETA</creatorcontrib><creatorcontrib>LAMMICH, SVEN</creatorcontrib><creatorcontrib>POSTINA, ROLF</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of the New York Academy of Sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>FAHRENHOLZ, FALK</au><au>GILBERT, SANDRA</au><au>KOJRO, ELZBIETA</au><au>LAMMICH, SVEN</au><au>POSTINA, ROLF</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>α-Secretase Activity of the Disintegrin Metalloprotease ADAM 10: Influences of Domain Structure</atitle><jtitle>Annals of the New York Academy of Sciences</jtitle><addtitle>Ann N Y Acad Sci</addtitle><date>2000-01-01</date><risdate>2000</risdate><volume>920</volume><issue>1</issue><spage>215</spage><epage>222</epage><pages>215-222</pages><issn>0077-8923</issn><eissn>1749-6632</eissn><abstract>: 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.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>11193153</pmid><doi>10.1111/j.1749-6632.2000.tb06925.x</doi><tpages>8</tpages></addata></record> |
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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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