Processing of protein precursors by a novel family of subtilisin-related mammalian endoproteases.

The recent identification of a novel family of mammalian endoproteases that carry out intracellular processing of protein precursors at dibasic sites has ended a search that began twenty-five years ago with the discovery of the first such precursor, proinsulin. The five proteases found thus far are all related to the yeast dibasic-specific endoprotease kex2, and include PC2, PC3/PC1, PC4, furin/PACE, and PACE4. All are Ca(2+)-dependent serine proteases with catalytic domains organized similarly to the bacterial subtilisins. The emerging characteristics of these endoproteases, including their tissue-specific expression, subcellular localization, and cleavage site selectivity, indicates that members of this family arose during evolution to process a diverse group of functionally distinct precursors in a highly specific, compartmentalized and regulated fashion.