{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T16:01:11Z","timestamp":1790524871217,"version":"4.1.0"},"reference-count":29,"publisher":"The Company of Biologists","issue":"7","license":[{"start":{"date-parts":[[1999,4,1]],"date-time":"1999-04-01T00:00:00Z","timestamp":922924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Fibrillin-1, the main component of 10-12 nm microfibrils of the extracellular matrix, is synthesized as profibrillin and proteolytically processed to fibrillin. The putative cleavage site has been mapped to the carboxy-terminal domain of profibrillin-1, between amino acids arginine 2731 and serine 2732, by a spontaneous mutation in this recognition site that prevents profibrillin conversion. This site contains a basic amino acid recognition sequence (R-G-R-K-R-R) for proprotein convertases of the furin\/PACE family. In this study, we use a mini-profibrillin protein to confirm the cleavage in the carboxy-terminal domain by both fibroblasts and recombinantly expressed furin\/PACE, PACE4, PC1\/3 and PC2. Site-directed mutagenesis of amino acids in the consensus recognition motif prevented conversion, thereby identifying the scissile bond and characterizing the basic amino acids required for cleavage. Using a PACE\/furin inhibitor, we show that wild-type profibrillin is not incorporated into the extracellular matrix until it is converted to fibrillin. Therefore, profibrillin-1 is the first extracellular matrix protein to be shown to be a substrate for subtilisin-like proteases, and the conversion of profibrillin to fibrillin controls microfibrillogenesis through exclusion of uncleaved profibrillin.<\/jats:p>","DOI":"10.1242\/jcs.112.7.1093","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T17:27:02Z","timestamp":1619371622000},"page":"1093-1100","source":"Crossref","is-referenced-by-count":79,"title":["Carboxy-terminal conversion of profibrillin to fibrillin at a basic site by PACE\/furin-like activity required for incorporation in the matrix"],"prefix":"10.1242","volume":"112","author":[{"given":"Michael","family":"Raghunath","sequence":"first","affiliation":[{"name":"1 Department of Physiological Chemistry and Pathobiochemistry"},{"name":"Department of Medical Physics and Biophysics 2 , , Germany"},{"name":"University of M\u00fcnster, M\u00fcnster 2 , , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Putnam","sequence":"additional","affiliation":[{"name":"The University of Texas-Houston Medical School 3 Department of Internal Medicine , , 6431 Fannin, MSB 1.614, Houston, Texas 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Ritty","sequence":"additional","affiliation":[{"name":"The University of Texas-Houston Medical School 3 Department of Internal Medicine , , 6431 Fannin, MSB 1.614, Houston, Texas 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Hamstra","sequence":"additional","affiliation":[{"name":"The University of Michigan 4 Department of Radiation Oncology , , Ann Arbor, Michigan 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Sook","family":"Park","sequence":"additional","affiliation":[{"name":"The University of Texas-Houston Medical School 3 Department of Internal Medicine , , 6431 Fannin, MSB 1.614, Houston, Texas 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Tsch\u00f6drich-Rotter","sequence":"additional","affiliation":[{"name":"Department of Medical Physics and Biophysics 2 , , Germany"},{"name":"University of M\u00fcnster, M\u00fcnster 2 , , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiner","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Medical Physics and Biophysics 2 , , Germany"},{"name":"University of M\u00fcnster, M\u00fcnster 2 , , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alnawaz","family":"Rehemtulla","sequence":"additional","affiliation":[{"name":"The University of Michigan 4 Department of Radiation Oncology , , Ann Arbor, Michigan 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianna M.","family":"Milewicz","sequence":"additional","affiliation":[{"name":"The University of Texas-Houston Medical School 3 Department of Internal Medicine , , 6431 Fannin, MSB 1.614, Houston, Texas 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1999,4,1]]},"reference":[{"key":"2024011223103904600_JOCES_112_7_1093C1","doi-asserted-by":"crossref","first-page":"25284","DOI":"10.1074\/jbc.271.41.25284","article-title":"Identification of a transferable sorting domain for the regulated pathway in the prohormone convertase PC2","volume":"271","author":"Creemers","year":"1996","journal-title":"J. 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