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To determine the precise role of PC1\/3 in proIAPP processing, Western blot analysis was performed on islets isolated from mice lacking PC1\/3 (PC1\/3\u2212\/\u2212). These islets contained not only fully processed IAPP as in PC1\/3+\/+ islets, but also elevated levels of a COOH-terminally unprocessed intermediate form, suggesting impaired processing at the COOH-terminus. Next, GH3 cells that do not normally express proIAPP or detectable levels of PC1\/3 or PC2 were cotransduced with adenoviruses expressing rat proIAPP and either PC2 or PC1\/3. As expected, in GH3 cells transduced to express only proIAPP, no processing was observed. Coexpression of proIAPP and PC2 resulted in production of mature IAPP, whereas in cells that coexpressed proIAPP and PC1\/3 only a 6-kDa intermediate was produced. We conclude that PC1\/3 is important for processing of proIAPP at the COOH-terminus, but in its absence, PC2 can initiate complete processing of proIAPP to IAPP by cleaving the precursor at either its NH2- or COOH-terminal cleavage sites.<\/jats:p>","DOI":"10.2337\/diabetes.53.1.141","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"141-148","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":100,"title":["Role of \u03b2-Cell Prohormone Convertase (PC)1\/3 in Processing of Pro-Islet Amyloid Polypeptide"],"prefix":"10.2337","volume":"53","author":[{"given":"Lucy","family":"Marzban","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine & British Columbia Research Institute for Children\u2019s and Women\u2019s Health, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genny","family":"Trigo-Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine & British Columbia Research Institute for Children\u2019s and Women\u2019s Health, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Pacific Northwest Research Institute, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe A.","family":"Halban","sequence":"additional","affiliation":[{"name":"Laboratoires de Recherche Louis Jeantet, University of Geneva Medical Center, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald F.","family":"Steiner","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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