It is well established that peptide hormones are synthesized as larger peptide precursors. Initially this was demonstrated by pulse-chase studies, in vitro synthesis, and immunoprecipitation (Docherty and Steiner, 1982; Loh and Gainer, 1983, for reviews), but molecular biology has now made the sequences of a large number of hormone precursors available, for example, proopiomelanocortin (Nakanishi et al., 1979), proenkephalin (Noda et al., 1982), provasopressin (Land et al., 1982), and prooxytocin (Land et al., 1983). These sequences show certain common features (Fig. 1); in particular, the hormone sequences are bracketed by pairs of basic amino acid residues such as Lys-Arg, Lys-Lys, or Arg-Arg. The precursor forms of these hormones generally lack biological activity, so that limited proteolysis at paired basic residues is necessary to generate the hormones, followed by exopeptidase activity to remove the Lys and Arg terminal residues, which are not found in the mature peptide hormones. Carboxypeptidases (Fricker and Snyder, 1983; Hook and Loh, 1984) and aminopeptidases (Gainer et al., 1984) have been described that are capable of such modifications. However, this discussion is confined to the initial proteolysis by endopeptidases. Cleavage may be followed by other modifications such as acetylation and amidation in order to produce biological potency (Loh and Gainer, 1983, for review).
KeywordsSecretory Granule Secretory Vesicle Intermediate Lobe Chromaffin Granule Basic Amino Acid Residue
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