Mammalian Neural and Endocrine Pro-Protein and Pro-Hormone Convertases Belonging to the Subtilisin Family of Serine Proteinases

Abstract

Conversion of pro-hormones and precursor proteins into biologically active peptides and proteins involves the concerted action of a number of convertases and posttranslation modification enzymes. The identification of the yeast convertase kexin as a prototype processing enzyme led to the discovery of the mammalian convertases designated furin, PCI and PC2. Whereas furin is ubiquitously expressed, PCI and PC2 are found only in endocrine and neural tissues and cell lines. In man and mouse, the genes coding for furin, PCI and PC2 reside on three different chromosomes. The analysis of the intracellular processing of PCI and PC2 and the removal of their pro-segment is presented, together with a summary of the cleavage specificity of these enzymes for precursors such as pro-opiomelanocortin (POMC) and human pro-renin. The distinct tissue distribution of PCI and PC2 and their coregulation with POMC in the pituitary neurointermediate lobe adds credence to their physiological role as convertases involved in the tissue-specific processing of precursor proteins.