Prohormone convertase PC5 is a candidate processing enzyme for prorenin in the human adrenal cortex.
We isolated a cDNA clone encoding the human prohormone convertase PC5 from human adrenal gland mRNA. The deduced protein sequence would encode a 915 amino acid preproPC5 that shares a very high degree of homology with previously cloned rat and mouse homologues. PC5 mRNA was detected in multiple human tissues, including the brain, adrenal and thyroid glands, heart, placenta, lung, and testes. PC5 mRNA was undetectable in the liver and was present at lower levels in skeletal muscle, kidney, pancreas, small intestine, and stomach. Co-transfection of human PC5 and human prorenin expression vectors in cultured GH4C1 cells led to secretion of active renin. The activation of human prorenin by PC5 depended on a pair of basic amino acids at positions 42 and 43 of the prorenin prosegment and occurred only in cells containing dense core secretory granules. Human PC5 was colocalized with renin by immunohistochemistry in the zona glomerulosa of the adrenal gland, suggesting that it could participate in the activation of a local renin-angiotensin system in the human adrenal cortex.
Mercure
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C
Laboratory of Molecular Biochemistry of Hypertension, Clinical Research Institute of Montreal, Quebec, Canada.
Jutras
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I
Day
R
R
Seidah
N G
NG
Reudelhuber
T L
TL
D000302:Adrenal Cortex / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D045702:Proprotein Convertase 5; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology*; D012697:Serine Endopeptidases / Q000302:isolation & purification*; D014162:Transfection
D045702:Proprotein Convertase 5; D012697:Serine Endopeptidases; D012083:Renin