Role of the prohormone convertase PC2 in the processing of proglucagon to glucagon

Abstract
Proglucagon is alternatively processed to glucagon in pancreatic α‐cells, or to glucagon‐like peptide‐1 in intestinal L cells. Here, the specificity of PC2, the major prohormone convertase of α‐cells, was examined both in vivo and in vitro. Adenovirus‐mediated co‐expression of proglucagon and PC2 in GH4C1 cells resulted in a pattern of processing products very similar to that observed in α‐cells. Oxyntomodulin, an intermediate in the processing of proglucagon, was quantitatively converted to glucagon in vitro by purified recombinant PC2, in combination with carboxypeptidase E. It is concluded that PC2 is able to act alone in the pancreatic pathway of proglucagon processing.