Studies on Processing Endoproteases of Biologically Active Peptide Precursors

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In endocrine and neuronal cells, many biologically active peptides are synthesized as larger precursors, which undergo limited endoproteolysis at paired basic amino acids to yield bioactive products. Recently, six endoproteases (furin, PC2, PC3, PC4, PACE4, and PC6) has been shown to be involved in this type of processing. In this study, we have shown the followings with respect to furin.1. We have discovered a mammalian cell line that lacks endoproteolytic activity due to mutations of furin. We have shown using this cell line that furin is the most important protease for processing of precursors of many proteins.2. Furin is mainly localized to the trans-Golgi network (TGN) within cells. We have shown that, for the TGN-localization of furin, its cytoplasmic domain is essential, and Ser and Tyr residues within this domain play an important role.