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 enco de a 915 amino acid preproPC5 that shares a very high degree of homolo gy with previously cloned rat and mouse homologues. PC5 mRNA was detec ted in multiple human tissues, including the brain, adrenal and thyroi d glands, heart, placenta, lung, and testes. PC5 mRNA was undetectable in the liver and was present at lower levels in skeletal muscle, kidn ey, pancreas, small intestine, and stomach. Cotransfection of human PC 5 and human prorenin expression vectors in cultured GH(4)Cl cells led to secretion of active renin. The activation of human prorenin by PCS 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 s ecretory granules. Human PC5 was colocalized with renin by immunohisto chemistry in the zona glomerulosa of the adrenal gland, suggesting tha t it could participate in the activation of a local renin-angiotensin system in the human adrenal cortex.