Ferric ions inhibit proteolytic processing of progastrin

Abstract

The gastrointestinal hormone gastrin is generated from an 80 amino acid precursor (progastrin) by cleavage after dibasic residues by prohormone convertase 1. Phosphorylation of Ser75 has previously been suggested, on the basis of indirect evidence, to inhibit cleavage of progastrin after Arg73Arg74. Gastrins bind two ferric ions with high affinity, and iron binding is essential for the biological activity of non-amidated gastrins in vitro and in vivo. This study directly investigated the effect of iron binding and of serine phosphorylation on the cleavage of synthetic progastrin-derived peptides. The affinity of synthetic progastrin55-80 for ferric ions, and the rate of cleavage by prohormon..