Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatostatin (SRIF) is a peptide hormone that is synthesized as part of a larger precursor, prepro-SRIF, consisting of a signal peptide and a proregion of 80-90 amino acids. The mature hormone exists as two different bioactive species. In addition to the most common form, which is a 14-residue peptide, there is also a 14-amino acid NH2-terminally extended form of the tetradecapeptide, SRIF-28. In mammals a single prepro-SRIF molecule undergoes tissue-specific processing to generate the mature hormone, whereas in some species of fish separate genes encode two distinct but homologous precursors, prepro-SRIF-I and -II, that give rise to SRIF-14 and -28, respectively. To investigate the molecular basis for differential processing of the prohormones, we have expressed their cDNAs in heterologous cells. Previously, we demonstrated that prepro-SRIF-I was efficiently and accurately processed in rat pituitary growth hormone (GH3) cells to generate the same hormone as synthesized in pancreatic islet D-cells, namely SRIF-14 (Stoller, T., and Shields, D. (1989) J. Biol. Chem. 264, 6922-6928). We have now compared the proteolytic processing of pro-SRIF-II to that of pro-SRIF-I in these cells. In contrast to pro-SRIF-I, pro-SRIF-II was neither processed nor secreted. Instead, greater than 70% of the precursor was degraded intracellularly in a post-trans Golgi network compartment which was inhibited by weak bases. Brefeldin A treatment prevented degradation, suggesting that turnover of the remaining pro-SRIF-II occurred after exit from the endoplasmic reticulum/intermediate compartment and prior to arrival at the trans Golgi network. The intracellular degradation of the precursor was unexpected, since heterologous cells which do not cleave prohormones generally secrete the unprocessed precursor. We speculate that unique structural domains within each precursor are recognized by the sorting apparatus in GH3 cells, thereby targeting the molecules to different intracellular organelles.
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PMID:Heterologous expression of preprosomatostatin. Intracellular degradation of prosomatostatin-II. 167 9

Prosomatostatin, the precursor of the hormone somatostatin, harbors an N-glycosylation site in its prodomain that has never been shown to be modified by the N-oligosaccharyl transferase (OST) of the endoplasmic reticulum (ER). The addition of Brefeldin A (BFA) to prosomatostatin transfected AtT20 cells leads to a quantitative glycosylation of the prohormone. Upon removal of the BFA the glycosylated hormone precursor is not deglycosylated, and is secreted after maturation of its oligosaccharide chain in the late secretory pathway. In addition, a significant proportion of the glycosylated hormone precursor remains in the cell. Since BFA is known to induce an effective collapse of the Golgi complex into the ER, the hypothesis that a prolonged exposure to the ER glycosylation machinery is responsible for the glycosylation was tested. No N-glycosylation was detected using a coupled in vitro transcription-translation system in the presence of canine pancreatic microsomes, indicating that rapid transit through the ER does not explain the lack of glycosylation observed in vivo in the absence of BFA. These observations show that co-translational glycosylation by OST becomes possible due to a still unidentified modification in the luminal environment brought about by the coalescence of the Golgi into the ER caused by BFA.
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PMID:Brefeldin A-induced prosomatostatin N-glycosylation in AtT20 cells. 1217 26