A member of the eukaryotic subtilisin family (PC3) has the enzymic properties of the type 1 proinsulin-converting endopeptidase

Author:

Bailyes E M1,Shennan K I J2,Seal A J2,Smeekens S P3,Steiner D F3,Hutton J C1,Docherty K2

Affiliation:

1. Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge CB2 2QR, U.K.

2. Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Birmingham. B15 2TH, U.K.

3. Howard Hughes Medical Institute and Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, U.S.A.

Abstract

PC3, a mammalian homologue of the yeast subtilisin-like proteinase Kex2, was expressed in Xenopus oocytes and its activity was characterized. PC3 cleaved human proinsulin at one of the two dibasic sites (KTRR32 but not LQKR65). The specificity, inhibitor profile, pH optimum (5.5) and Ca(2+)-dependence (K0.5 = 2.5-3 mM) paralleled those of the insulin-granule type 1 endopeptidase activity, suggesting a role for PC3 in the conversion of prohormones.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry

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