The Functional Maturation of A Disintegrin and Metalloproteinase (ADAM) 9, 10, and 17 Requires Processing at a Newly Identified Proprotein Convertase (PC) Cleavage Site.

The Journal of Biological Chemistry
Eitan WongIrit Sagi

Abstract

Proenzyme maturation is a general mechanism to control the activation of enzymes. Catalytically active members of the A Disintegrin And Metalloprotease (ADAM) family of membrane-anchored metalloproteases are synthesized as proenzymes, in which the latency is maintained by their autoinhibitory pro-domains. A proteolytic processing then transforms the proenzyme into a catalytically active form. The removal of the pro-domain of ADAMs is currently thought to depend on processing at a canonical consensus site for the proprotein convertase Furin (RXXR) between the pro- and the catalytic domain. Here, we demonstrate that this previously described canonical site is a secondary cleavage site to a prerequisite cleavage in a newly characterized upstream PC site embedded within the pro-domain sequence. The novel upstream regulatory site is important for the maturation of several ADAM proenzymes. Mutations in the upstream regulatory site of ADAM17, ADAM10, and ADAM9 do not prevent pro-domain processing between the pro- and metalloprotease domain, but nevertheless, cause significantly reduced catalytic activity. Thus, our results have uncovered a novel functionally relevant PC processing site in the N-terminal part of the pro-domain that is ...Continue Reading

References

Jul 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·H E Van Wart, H Birkedal-Hansen
Feb 1, 1996·The Journal of Cell Biology·G WeskampC P Blobel
Jun 27, 1998·The Journal of Biological Chemistry·F LoechelU M Wewer
Jul 17, 1998·Current Opinion in Chemical Biology·D F Steiner
Sep 25, 1998·The Journal of Biological Chemistry·L LumC P Blobel
Jan 5, 1999·Science·H QiS Artavanis-Tsakonas
Jan 28, 1999·The Journal of Biological Chemistry·M RoghaniC P Blobel
May 18, 1999·The American Journal of Pathology·K IbaU M Wewer
May 9, 2000·The Journal of Biological Chemistry·P ReddyR A Black
Aug 2, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A AndersF Fahrenholz
Sep 19, 2002·The Journal of Biological Chemistry·Yufang ZhengCarl P Blobel
Feb 27, 2004·Protein Engineering, Design & Selection : PEDS·Peter DuckertNikolaj Blom
Mar 3, 2004·The Journal of Cell Biology·Umut SahinCarl P Blobel
Apr 22, 2004·The Journal of Biological Chemistry·Patricia E GonzalesMarcos E Milla
Mar 8, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Caitriona A BuckleyStewart J Levine
Feb 17, 2006·Journal of Biochemical and Biophysical Methods·Fusinita van den Ent, Jan Löwe
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Ariel SolomonIrit Sagi
Mar 11, 2009·Molecular and Cellular Biology·Victor GuaiquilCarl P Blobel
Apr 26, 2011·Journal of Structural Biology·Ariel ErijmanYoav Peleg
Oct 19, 2013·Biochimica Et Biophysica Acta·Jeanette SchwarzAthena Chalaris

❮ Previous
Next ❯

Citations

Nov 3, 2015·Progress in Neurobiology·Paul Saftig, Stefan F Lichtenthaler
Sep 20, 2016·JCI Insight·Eirini KefaloyianniAndreas Herrlich
Jun 22, 2017·Biochimica Et Biophysica Acta. Molecular Cell Research·Maxim LevinIrit Sagi
Feb 1, 2018·Pharmaceuticals·Rafaela PeronMárcia Regina Cominetti
Oct 26, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anne-Sophie CabronFriederike Zunke
Jul 25, 2019·Experimental Biology and Medicine·Tom Cm Seegar, Stephen C Blacklow
Feb 26, 2016·Current Opinion in Hematology·Toni M AntalisMarguerite S Buzza
Feb 16, 2020·The Journal of Biological Chemistry·Gisela WeskampCarl P Blobel
Aug 6, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rielana WichertChristoph Becker-Pauly
Apr 14, 2020·Expert Opinion on Drug Discovery·Prashant R MurumkarMange Ram Yadav
May 6, 2016·The Biochemical Journal·Gisela von HovenMatthias Husmann
Apr 4, 2017·Frontiers in Molecular Neuroscience·Kristina Endres, Thomas Deller
Jun 18, 2017·Biochemical Society Transactions·Alexandra L MatthewsMichael G Tomlinson
Feb 19, 2020·Translational Psychiatry·Balmiki RayDebomoy K Lahiri
Sep 12, 2020·International Journal of Molecular Sciences·Mazin A Al-Salihi, Philipp A Lang
Apr 15, 2017·Journal of Alzheimer's Disease : JAD·Xiang-Zhen YuanLan Tan
Sep 23, 2018·Nature Reviews. Immunology·Bart N LambrechtHamida Hammad
Oct 12, 2019·Cells·Dirk Schmidt-Arras, Stefan Rose-John
Jun 27, 2019·Cellular and Molecular Life Sciences : CMLS·Hung-En HsiaStefan F Lichtenthaler
Apr 16, 2020·Critical Reviews in Biochemistry and Molecular Biology·Lise BoonGhislain Opdenakker
Sep 8, 2017·Frontiers in Molecular Biosciences·Tomer WeizmanAmir Aharoni
Mar 20, 2018·Cellular and Molecular Life Sciences : CMLS·Victor O OriaOliver Schilling
Jul 18, 2018·Frontiers in Immunology·Alexandra L MatthewsMichael G Tomlinson
Apr 9, 2020·Frontiers in Immunology·Timothy M SmithRebecca K Martin
Oct 25, 2020·International Journal of Molecular Sciences·Cheng-Wei ChouYuh-Pyng Sher
Jan 29, 2021·The Journal of Biological Chemistry·Gisela WeskampCarl P Blobel
Feb 13, 2021·Cellular and Molecular Life Sciences : CMLS·Tatsuo KawaiSatoru Eguchi
Feb 14, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Matteo CalligarisSimone Dario Scilabra
Jun 3, 2021·International Journal of Molecular Sciences·Francesca TosettiMaria Raffaella Zocchi
Jul 3, 2021·International Journal of Molecular Sciences·Neale HarrisonMichael G Tomlinson
Jul 1, 2021·Biological Chemistry·Mazin Al-SalihiPhilipp A Lang
Jul 17, 2021·Frontiers in Molecular Biosciences·Keron W J RoseDirk Hubmacher
May 19, 2018·Chemical Reviews·Joan L ArolasF Xavier Gomis-Rüth
Jul 15, 2017·Biochimica Et Biophysica Acta. Molecular Cell Research·Friederike Zunke, Stefan Rose-John

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.