Human somatostatin I: sequence of the cDNA.

Abstract

RNA has been isolated from a human pancreatic somatostatinoma and used to prepare a cDNA library. After prescreening, clones containing somatostatin I sequences were identified by hybridization with an anglerfish somatostatin I-cloned cDNA probe. From the nucleotide sequence oftwo ofthese clones, we have deduced an essentially full-length mRNA sequence, including the preprosomatostatin coding region, 105 nucleotides from the 5' untranslated region and the complete 150-nucleotide 3' untranslated region. The coding region predicts a 116-amino acid precursor protein (Mr,12,727) that contains somatostatin-14 and -28 at its COOH terminus. The predicted amino acid sequence of human somatostatin-28 is identical to that of somatostatin-28 isolated from the porcine and ovine species. A comparison of the amino acid sequences ofhuman and anglerfish preprosomatostatin I indicated that the COOH-terminal region encoding somatostatin-14 and the adjacent 6 amino acids are highly conserved, whereas the remainder of the molecule, including the signal peptide region, is more divergent. However, many of the amino acid differences found in the pro region of the human and anglerfish proteins are conservative changes. This suggests that the propeptides have a similar secondary structure, which in turn may imply a biological function for this region of the molecule.Somatostatin is a 14-amino acid polypeptide that inhibits the secretion of other polypeptides and hormones, including growth hormone, insulin, glucagon, and gastrin (reviewed in ref. 1). It occurs in the pancreas, stomach, and small intestine, as well as in the central nervous system. Its presence in neuronal tissue (2) and its apparent neurophysiological action (3) has led to the postulate that somatostatin is also a neurotransmitter.Higher Mr forms of somatostatin immunoreactivity have been detected (4). Studies (5) ofthe biosynthesis ofsomatostatin in cultured rat pancreatic islets have suggested that the larger immunoreactive species are somatostatin precursors. A 28-amino acid peptide containing the somatostatin moiety has been isolated from porcine intestine (6) and hypothalamus (7) and more recently from ovine hypothalamus (8).We recently have cloned and sequenced somatostatin cDNA from the endocrine pancreas of anglerfish (9). The nucleotide sequence of the coding region predicted a 121-amino acid polypeptide containing somatostatin at its COOH terminus. This polypeptide is presumed to be the first somatostatin precursor. We also discovered another cDNA from anglerfish that encoded a 125-amino acid polypeptide that contained a somatostatin-like moiety at its COOH terminus. This somatostatin differs from the former somatostatin in two of the 14 amino acids (Tyr in place of Phe-7 and Gly in place of Thr-10). Therefore, we termed the classical somatostatin sequence somatostatin I and the novel sequence somatostatin II. Somatostatin II has been chemically synthesized and shown to inhibit selectively insulin release with no detectable effect on glucagon releas...

New insight into the molecular evolution of the somatostatin family

“…10;Veber et al, 1979;Flohr et al, 2002;Labarrère et al, 2003;Chatenet et al, 2004), so that UII has been first described as a somatostatin-like peptide (Pearson et al, 1980). In addition, it has been found that the organization of the precursors of UII, SS1 and related peptides are globally similar (Shen et al, 1982;Ohsako et al, 1986;Tostivint et al, 1996;Coulouarn et al, 1998Coulouarn et al, , 1999. Nevertheless, characterization of the cDNA encoding the UII precursor has shown that prepro-UII and prepro-SS1 do not exhibit appreciable sequence identity (Ohsako et al, 1986;Coulouarn et al, 1998Coulouarn et al, , 1999 and hence, it was concluded that the UII and SS1 precursors were probably not derived from a common ancestral gene.…”

Characterization of three peptides derived from prosomatostatin [prosomatostatin-(1–63)-, -(65–76)- and -(79–92)-peptides] in a human pancreatic tumour

“…The composition of the peptide from peak 3 indicated probable identity with prosomatostatin-(1-63)-peptide. With the exception of a slightly high value for glutamic acid/glutamine and a slightly low value for proline, the agreement between the composition measured and that predicted from the nucleotide sequence of the prepro- somatostatin gene (Shen et al, 1982;Shen & Rutter, 1984) was good. Cleavage of prosomatostatin-(1-63)-peptide with Armillaria mellea proteinase generated five peptide fragments, which were separated by reversephase h.p.l.c.…”

“…Tumours in which somatostatin-producing D-cells represent a majority cell type ('somatostatinomas') are rare, but have been found most often in the pancreas (Ganda et al, 1977;Larsson et al, 1977;Krejs et al, 1979;Pipeleers et al, 1979;Wright et al, 1980). The structure of the biosynthetic precursor of somatostatin (preprosomatostatin) in the human may be deduced from the nucleotide sequence of a cloned cDNA prepared from a human pancreatic tumour (Shen et al, 1982), and the structure of the gene has been determined from DNA fragments from a human genomic library (Shen & Rutter, 1984). Human preprosomatostatin is a protein of 116 amino acids that contains the sequence of somatostatin-14 at its C-terminus.…”

AIP and the somatostatin system in pituitary tumours

“…(Lamberts 1988, Schettini 1991, Martel et al 2012. SST gene is transcribed to yield the pre-pro somatostatin-encoding mRNA (Shen et al 1982, Naylor et al 1983, Shen & Rutter 1984, which is subsequently translated and the protein is processed to give rise to SST, an active peptide of 28 amino acids (Schally et al 1980, Brown et al 1981, which is commonly further processed into a shorter active variant of 14 amino acids, generally named SST-14 or simply SST (Epelbaum 1986, Martel et al 2012.…”