Enzymes Processing Somatostatin-Precursors, The Somatostatin-28 Convertase of Rat Brain, A System Converting Somatostatin-28 to Both Somatostatins-14 and -28(1–12)
In the biosynthetic pathways of neuropeptides both co- and post-translational events are essential in confering to these messengers their biological activity. Regulation of these mechanisms may be critical in giving rise to diversity in the products derived from the processing of a single, but multipotential, biosynthetic precursor (Eipper and Mains, 1980; Benoit et al., 1982a; Kimura et al., 1986). Of particular importance is the proteolysis which allows the active fragments to be released from their larger proforms. Cleavage of peptide bonds appears to occurs generally at loci consisting in basic amino acids (Arg or Lys) arranged within the precursor sequence as doublets (Nakanishi et al., 1979), sometime as triplets (Craig et al., 1982) or even as quadruplets (Nakanishi et al., 1979; Furutani et al., 1983). Attempts to characterize the enzyme(s) possibly involved in these cleavages were hampered by difficulties in obtaining sufficient amounts of purified hormone precursors. The biosynthetic system of somatostatin-14 (S-14), a tetradecapeptide found both in the central nervous system and in the gastro-intestinal tract, is particularly well-suited for such studies since, in mammals, the peptide hormone seems to derive from a single precursor (Morel et al., 1983). Its structure was determined in various systems through the sequencing of cDNA, to the corresponding mRNAs (Hobart et al., 1980; Goodman et al., 1983). In all cases, the S-14 molecule occupies the COOH-terminal end of the precursor and is preceded at positions -1 and -2 by a basic doublet (Lys-1, Arg-2). Amino terminal extension of this particular structure leads to an octaeicosapeptide, somatostatin-28 (S-28), which includes in its sequence both the NH2-terminal fragment, called S-28 (1–12) and S-14. Therefore, in theory, selective excision of the Arg Lys doublet should release stoichiometric amounts of both S-14 and S-28 (1–12). The corollary is that the octaeicosapeptide S-28 was considered as a possible common precursor to both the NH2- and COOH- terminal dodeca- and tetradeca- peptides respectively (see for a discussion Patel Y.C., 1986).
KeywordsPeptide Bond Granule Membrane Neurosecretory Granule Cationic Resin Biosynthetic System
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