A member of the eukaryotic subtilisin family (PC3) has the enzymic properties of the type 1 proinsulin-converting endopeptidase.
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.
Bailyes
E M
EM
Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, U.K.
Shennan
K I
KI
Seal
A J
AJ
Smeekens
S P
SP
Steiner
D F
DF
Hutton
J C
JC
Docherty
K
K
D000818:Animals; D000911:Antibodies, Monoclonal; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008845:Microinjections; D012333:RNA, Messenger / Q000378:metabolism; D013379:Substrate Specificity; D013381:Subtilisins / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D010450:Endopeptidases; D013381:Subtilisins; C054196:proinsulin endopeptidase I