PC1 and PC2 are proprotein convertases capable of cleaving proopiomelanocortin at distinct pairs of basic residues

Abstract

A recombinant vaccinia virus vector was used to coexpress the two candidate mouse prohormone convertases, PCI and PC2, together with mouse proopiomelanocortin (POMC) in the constitutively secreting cell line BSC-40 and in the endocrine tissue-derived cell lines PC12 and AtT-20, which exhibit regulated secretion. Monitoring of POMC processing demonstrated the distinct cleavage specificities of PCI and PC2, since in the cell lines analyzed (i) PCI cleaves POMC into cortkotropin and β-lipotropin, (ii) PC2 cleaves POMC into β-endorphin, an N-terminally extended cortkotropin containing the joining peptide, and either αMSH or desacetyl-αMSH, and (in) PC2 cleaves POMC at the five pairs of bask residues analyzed, whereas PCI cleaves two of them preferentially, suggesting that PC2 has a broader spectrum of activity than PCI. These data are consistent with our hypothesis on the physiological role of PCI and PC2 as distinct proprotein convertases acting alone or together to produce a set of tissue-specific maturation products in the brain and in peripheral tissues.