The Possible Role of Plasma Kallikrein in Pro-Hormone and Pro-Enzyme Processing

Abstract

It is now clear that a great number of proteins are originally synthesized as large polypeptide precursors containing within their sequence biologically active peptides. These “motifs” are usually sandwiched between either single or pairs of basic residues (Lazure et al., 1983). Post-translational processing of these precursors involves the participation of a number of enzymes which shape these biologically active segments into their final mature form(s). One of the least well understood maturation step concerns the protease(s) responsible for the “trypsin-like” limited proteolysis occuring at either pairs of basic residues or post-single basic residues. Recently, a number of candidate mammalian processing enzymes have been proposed. These include an aspartyl protease (Parish et al., 1986), metalloproteases (Clamagirand et al., 1987; Hutton et al., 1987), thiol protease (Fletcher et al., 1981) and serine proteases (Lindberg et al., 1984; Cromlish et al., 1986a,b; Seidah et al., 1986). So far, evidence for the participation of these candidate proteases in pro-protein processing has been indirect, based on their localization in secretory granules and/or their “in vitro” cleavage of either model substrates or pro-hormone precursors at sites identical to those cleaved “in vivo.”