Proteolytic processing of human prorenin in renal and non-renal tissues.
Previous studies have demonstrated that the mouse proprotein convertase PC1 (mPC1) accurately cleaves human prorenin to generate active renin and that this processing event appears to require co-packaging in secretory granules. In the current study, we have tested human PC1 (hPC1; also called PC3) for its ability to activate human prorenin. Our results suggest that while hPC1 is capable of carrying out the specific cleavage of human prorenin, it does so at a reduced efficiency as compared to mPC1. This difference is due to sequences in the carboxy-terminus of PC1 as demonstrated by the activity of hybrid hPC1/mPC1 molecules. These studies demonstrate that PC1 cleavage of prorenin can occur in humans and identify a functionally important region in the hPC1 protein for this interaction. Moreover, the localization of PC1 in human tissues suggests that it may participate in the generation of active renin in the adrenal medulla and possibly in certain adrenal tumors.
Reudelhuber
T L
TL
Laboratory of Molecular Biochemistry of Hypertension, Clinical Research Institute of Montreal, Quebec, Canada.
Ramla
D
D
Chiu
L
L
Mercure
C
C
Seidah
N G
NG
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002460:Cell Line; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D045664:Proprotein Convertase 1; D043484:Proprotein Convertases; D011499:Protein Processing, Post-Translational; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D014162:Transfection
D004792:Enzyme Precursors; D043484:Proprotein Convertases; C473656:Pcsk1 protein, mouse; D045664:Proprotein Convertase 1; D016282:Aspartic Acid Endopeptidases; D012083:Renin