AUTOPROTEOLYTIC ACTIVATION OF THE MOUSE PROHORMONE CONVERTASE-MPC1

In this study the activation of the prohormone convertase mPC1 was det ermined. Expression and characterization of catalytic domain mutations (Ser382 to Ala or His208 to Ala) in the prohormone convertase mPC1, u nequivocally demonstrated that pro-region cleavage proceeds by an auto catalytic mechanism. Furthermore, these results suggest that autoprote olysis may be the result of an intramolecular reaction, since proregio n processing of the active-site mutant could not be complemented by th e overexpression of active furin or PC1. Additionally coexpression of a cleavage-site mutant (Arg(110)-Ala) with the substrate prorelaxin fu rther demonstrated that autoproteolysis is required for the full activ ity of PC1. (C) 1994 Academic Press, Inc.