{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:58:12Z","timestamp":1789545492579,"version":"build-2803163510"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"34","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,8,26]]},"abstract":"<jats:p>\n                    Furin is a proprotein convertase which activates a variety of regulatory proteins in the constitutive exocytic and endocytic pathway. The effect of genetic ablation of\n                    <jats:italic>fur<\/jats:italic>\n                    was studied in the endocrine pancreas to define its physiological function in the regulated secretory pathway.\n                    <jats:italic>Pdx1-Cre<\/jats:italic>\n                    \/loxP furin KO mice show decreased secretion of insulin and impaired processing of known PC2 substrates like proPC2 and proinsulin II. Both secretion and PC2 activity depend on granule acidification, which was demonstrated to be significantly decreased in furin-deficient \u03b2 cells by using the acidotrophic agent 3-(2,4-dinitroanilino)-3\u2032amino-\n                    <jats:italic>N<\/jats:italic>\n                    -methyldipropylamine (DAMP). Ac45, an accessory subunit of the proton pump V-ATPase, was investigated as a candidate substrate. Ac45 is highly expressed in islets of Langerhans and furin was able to cleave Ac45\n                    <jats:italic>ex vivo<\/jats:italic>\n                    . Furthermore, the exact cleavage site was determined. In addition, reduced regulated secretion and proinsulin II processing could be obtained in the insulinoma cell line \u03b2TC3 by downregulation of either furin or Ac45. Together, these data establish an important role for furin in regulated secretion, particularly in intragranular acidification most likely due to impaired processing of Ac45.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0800340105","type":"journal-article","created":{"date-parts":[[2008,8,19]],"date-time":"2008-08-19T23:52:10Z","timestamp":1219189930000},"page":"12319-12324","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":78,"title":["Role of furin in granular acidification in the endocrine pancreas: Identification of the V-ATPase subunit Ac45 as a candidate substrate"],"prefix":"10.1073","volume":"105","author":[{"given":"Els","family":"Louagie","sequence":"first","affiliation":[{"name":"Departments of *Human Genetics, Box 602, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil A.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Departments of *Human Genetics, Box 602, and"},{"name":"Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy","family":"Flamez","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Medicine, Universit\u00e9 Libre de Bruxelles, Route de Lennik 808, B-1070 Brussels, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton J. M.","family":"Roebroek","sequence":"additional","affiliation":[{"name":"Departments of *Human Genetics, Box 602, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A.","family":"Bright","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0XY, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Meulemans","sequence":"additional","affiliation":[{"name":"Departments of *Human Genetics, Box 602, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel","family":"Quintens","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology, Katholieke Universiteit Leuven, Gasthuisberg O\/N 1, Herestraat 49, B-3000 Leuven, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro L.","family":"Herrera","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Rue Michel-Servet 1, CH-1211 Geneva 4, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans","family":"Schuit","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology, Katholieke Universiteit Leuven, Gasthuisberg O\/N 1, Herestraat 49, B-3000 Leuven, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim J. 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