PROTEOLYTIC PROCESSING OF HUMAN PRORENIN IN RENAL AND NONRENAL TISSUES

Proteolytic processing of human prorenin in renal and non-renal tissue s. Previous studies have demonstrated that the mouse proprotein conver tase PC1 (mPC1) accurately cleaves human prorenin to generate active r enin and that this processing event appears to require co-packaging in secretory granules. In the current study, we have tested human PC1 (h PC1; also called PC3) for its ability to activate human prorenin. Our results suggest that while hPC1 is capable of carrying out the specifi c cleavage of human prorenin, it does so at a reduced efficiency as co mpared to mPC1. This difference is due to sequences in the carboxy-ter minus of PCI as demonstrated by the activity of hybrid hPC1/mPC1 molec ules. These studies demonstrate that PC1 cleavage of prorenin can occu r in humans and identify a functionally important region in the hPC1 p rotein for this interaction. Moreover, the localization of PC1 in huma n tissues suggests that it may participate in the generation of active renin in the adrenal medulla and possibly in certain adrenal tumors.