ENDOPROTEASES OTHER THAN FURIN HAVE A ROLE IN HEPATIC PROPROTEIN PROCESSING

The enzyme or enzymes responsible for dibasic-directed proprotein proc essing in the liver have not yet been unequivocally identified, althou gh there are a number of potential candidates. We have compared a Kex2 -like proalbumin convertase activity present in rat liver ER/Golgi mem branes with recombinant furin, a candidate hepatic convertase. Using a series of mutant recombinant proalbumins as substrates the biochemica lly identified convertase and furin had very similar specificities wit h both preferring a substrate with an ArgXaaArgArg processing motif. K inetic studies with normal and -4R proalbumin suggested however that t he proalbumin convertase was not identical to furin. This was confirme d in immunoabsorption studies which demonstrated that furin only accou nts for approximately half of the convertase activity. Therefore at le ast two proprotein convertases with overlapping specificities are invo lved in hepatic proprotein processing.