THE NEUROENDOCRINE POLYPEPTIDE 7B2 IS AN ENDOGENOUS INHIBITOR OF PROHORMONE CONVERTASE PC2

The subtilisin-like prohormone convertase PC2 and the polypeptide 7B2 (an intracellularly cleaved protein of unknown function) are both sele ctively present in the regulated secretory pathway of neurons and endo crine cells. Here we demonstrate that intact recombinant 7B2 is a pote nt inhibitor of PC2 and prevents proPC2 cleavage in vitro, whereas the 7B2 cleavage product is virtually inactive. The PC2-related proteinas e PC1/PC3 is not inhibited by 7B2. Furthermore, the carboxyl-terminal half of the 7B2 protein sequence is distantly related to the so-called potato inhibitor I family (which includes subtilisin inhibitors). Our findings indicate that 7B2 is a physiological inhibitor of PC2 and ma y provide alternative avenues for the manipulation of peptide hormone levels.