THE SPECIFICITY OF THE NEUROENDOCRINE CONVERTASE PC3 IS DETERMINED BYRESIDUES NH2-TERMINAL AND COOH-TERMINAL TO THE CLEAVAGE SITE

The Kex2-like convertase PC3 (PC1) has been implicated in the processi ng of a number of prohormones and proneuropeptides. In order to be abl e to more accurately predict substrates for PC3 its specificity was de fined using recombinant proalbumins and synthetic peptide substrates. P2P1 and P4P1 dibasic sites were cleaved with similar efficiencies how ever there were specific restrictions on amino acids NH2- and COOH-ter minal to the cleavage site. His was disallowed at P-2 and basic residu es were forbidden at P-1'. The presence of a charged residue at P-2' e ither completely prevented (Arg) or seriously impaired (Glu) cleavage by PC3 and the presence of a P-4 Arg did not significantly increase it s activity.