title: Role of cathepsin B as prorenin processing enzyme in human kidney.
abstract: Renin is synthesized from an inactive precursor, prorenin, through cleavage at a pair of basic amino acids catalyzed by prorenin processing enzyme (PPE). A lysosomal protease, cathepsin B, has been suggested to be a strong candidate for PPE. However, there still remains a possibility that other protease(s) can also catalyze prorenin processing. We studied the subcellular distribution of PPE in human renal cortex using pure recombinant prorenin as a PPE assay substrate. PPE and renin activities, and cathepsin B activity and protein were colocalized in the lysosomal fraction. The PPE activity was completely inhibited by a cathepsin B specific inhibitor, CA074. Taken together with the immunohistochemical data showing that cathepsin B and PPE are colocalized in dense secretory granules of juxtaglomerular cells of kidney, we conclude that cathepsin B is the authentic PPE in human kidney.
authors.affiliation: Third Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shinagawa
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: E
authors.initials: E
authors.lastname: Kominami
authors.forename: Y
authors.initials: Y
authors.lastname: Doi
authors.forename: K
authors.initials: K
authors.lastname: Hashiba
authors.forename: K
authors.initials: K
authors.lastname: Yano
authors.forename: W A
authors.initials: WA
authors.lastname: Hsueh
authors.forename: K
authors.initials: K
authors.lastname: Murakami
mesh_terms: D002384:Catalysis; D002401:Cathepsin B / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007672:Kidney Cortex / Q000201:enzymology* / Q000648:ultrastructure; D012083:Renin / Q000096:biosynthesis*; D013347:Subcellular Fractions / Q000201:enzymology; D013379:Substrate Specificity
chemical_list: D003546:Cysteine Endopeptidases; C063281:prorenin processing enzyme; D002401:Cathepsin B; D012083:Renin