AUTOPROTEOLYTIC ACTIVATION OF THE MOUSE PROHORMONE CONVERTASE-MPC1

In this study the activation of the prohormone convertase mPC1 was determined. Expression and characterization of catalytic domain mutations (Ser382 to Ala or His208 to Ala) in the prohormone convertase mPC1, unequivocally demonstrated that pro-region cleavage proceeds by an autocatalytic mechanism. Furthermore, these results suggest that autoproteolysis may be the result of an intramolecular reaction, since proregion processing of the active-site mutant could not be complemented by the overexpression of active furin or PC1. Additionally coexpression of a cleavage-site mutant (Arg(110)-Ala) with the substrate prorelaxin further demonstrated that autoproteolysis is required for the full activity of PC1. (C) 1994 Academic Press, Inc.