A new prosomatostatin-derived peptide reveals a pattern for prohormone cleavage at monobasic sites.

@article{Benoit1987ANP,
  title={A new prosomatostatin-derived peptide reveals a pattern for prohormone cleavage at monobasic sites.},
  author={Robert Benoit and Nicholas Ling and Frederick Stephen Esch},
  journal={Science},
  year={1987},
  volume={238 4830},
  pages={
          1126-9
        }
}
Cleavage of the peptide bonds of preprosomatostatin at basic residues near the carboxyl terminus yields somatostatin-14, somatostatin-28, and somatostatin-28 (1-12). However, little is known about the molecular forms derived from the amino terminal portion of the precursor, even though this part of the prohormone is highly conserved through evolution. By using an antibody against the amino terminus of prosomatostatin, a decapeptide with the structure Ala-Pro-Ser-Asp-Pro-Arg-Leu-Arg-Gln-Phe… 
Peptides derived by processing of rat prosomatostatin near the amino-terminus: characterization, tissue distribution, and release.
TLDR
This study has developed an antibody directed against the N-terminal segment of pro-S-(1-10) capable of detecting peptides extended at the C-terminus of prosomatostatin to characterize N-Terminal processing of ratpro-S.
Prosomatostatin processing in Neuro2A cells
TLDR
The hypothesis that the proline residue near the processing site for somatostatin-14 production is an important structural feature for conferring on the cleavage domain the adequate conformation for accessibility to processing enzymes and permitting production of equivalent amounts of both hormones is supported.
Prosomatostatin is proteolytically processed at the amino terminal segment by subtilase SKI-1
TLDR
Using a vaccinia virus expression system along with HPLC and radioimmunoassays, it is observed that overexpression of recombinant SKI-1 in COS-1 and HEK-293 cells significantly increased the production of PSST[1-10].
Endopeptidases and prohormone processing
TLDR
Recent advances that have been made in the characteristisation of proteolytic processing enzymes are described and new approaches that may lead to better understanding of the mechanisms involved are discussed.
The tissue-specific processing of Pro-ACTH/Endorphin recent advances and unsolved problems
TLDR
The purification and cloning of several peptide-processing enzymes, including KEX-1, KEX2, carboxypeptidase E, and peptidyl-glycine alpha-amidating monooxygenase, have provided important information about intracellular peptide processing, and are beginning to provide information about the sorting of soluble and membrane-associated components of secretory granules.
Elephantfish proinsulin possesses a monobasic processing site.
TLDR
Examination of the flanking sequences around this site shows that a typical endocrine/neuroendocrine PC3 conversion enzyme should still be able to cleave, as the general requirements for precursor processing at a monobasic site are satisfied.
Elimination of the carboxy-terminal sequences of parathyroid hormone-related protein 1-173 increases production and secretion of the truncated forms.
TLDR
The studies suggest that the carboxy-terminal sequence of PTHrP 1-173 is responsible for the intracellular degradation of this polypeptide, which may be the endogenous cellular mechanism that regulates the amount of processed and secreted PTHRP.
Prosomatostatin-derived antrin is present in gastric D cells and in portal blood.
TLDR
Data now show that in both rats and humans this new molecular form is concentrated in the D cell of the gastrointestinal mucosa together with somatostatin-28(1-12) and the highest concentration of antrin immunofluorescent cells is located in the mucosa of the gastric antrum.
A Conserved α-Helix at the Amino Terminus of Prosomatostatin Serves as a Sorting Signal for the Regulated Secretory Pathway*
TLDR
Deletion of the PSST-(3–15) segment blocked regulated secretion and rerouted PSST for constitutive secretion as unprocessed precursor, and processing was shifted to the early compartments of the secretory pathway rather than storage granules and was relatively inefficient.
N-terminal sequence analysis of atrial granule serine proteinase purified by affinity chromatography
TLDR
The sequence determined, XXPEAAGLPG[R, L]GNPVP[F, G]R[Q, I]XY[G, E]XR(N, A]V, indicates that the atrial enzyme is unique, showing little sequence homology to other proteins in the database.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 37 REFERENCES
Neuropeptides derived from prosomatostatin that do not contain the somatostatin-14 sequence
TLDR
Two neuropeptides reacting with antibodies directed against the C-terminal region of somatostatin 28(1-12) were purified to homogeneity from rat brain extracts and established their aminoterminal structure as Ala- pro-Ser-Asp-Pro-Arg-Leu- Arg-Gln-Phe-X- Gln-Lys and pre-proSS25-100.
Rat pre-prosomatostatin. Structure and processing by microsomal membranes.
TLDR
The high level of conservation between rodents and humans of the entire pre-prosomatostatin molecule further suggests the possibility of biologic functions of the NH2-terminal portions of prosom atostatin.
Enzymes processing somatostatin precursors: an Arg-Lys esteropeptidase from the rat brain cortex converting somatostatin-28 into somatostatin-14.
TLDR
It is concluded that this Arg-Lys esteropeptidase from the brain cortex may be involved in the in vivo processing of the somatostatin-28 fragment of prosom atostatin into somatOSTatin-14, the former species being an obligatory intermediate in a two-step proteolytic mechanism leading to somatstatin- 14.
Review-hypothesisThe processing of peptide precursors: ‘Proline-directed arginyl cleavage’ and other monobasic processing mechanisms
TLDR
On the basis of this ‘proline-directed arginyl cleavage’ it is discussed how the conformation of the peptide backbone might be important for this type of cleavage and it is suggested that tissue-specific expression of different processing enzymes, e.g. dibasic and monobasic specific forms, might explain the tissue- specific processing of precursors.
Isolation and characterization of proSS1–32, a peptide derived from the N‐terminal region of porcine preprosomatostatin
TLDR
The postulated cleavage site in porcine prosomatostatin is a Leu‐Leu bond between residues 32 and 33, thus confirming previous studies of the processing of the somatostAT precursor in the rat and transgenic mouse.
Primary structure of ovine hypothalamic somatostatin-28 and somatostatin-25.
TLDR
Their structures were established by subjecting the native peptides to direct sequence analysis in a Beckman 890C sequencer and identifying the released phenylthiohydantoin derivatives by high-performance liquid chromatography.
Presence of somatostatin-28-(1-12) in hypothalamus and pancreas.
TLDR
It is concluded that the prosomatostatin fragment Ser-Ala-Asn-Ser- asn-Pro-AlA-Met- ala- met-ala-pro-Arg-Glu-OH is present in both rat hypothalamus and rat pancreas.
The processing of peptide precursors
TLDR
On the basis of this ‘proline‐directed arginyl cleavage’ it is discussed how the conformation of the peptide backbone might be important for this type of cleavage and it is suggested that tissue‐specific expression of different processing enzymes, e.g. dibasic and monobasic specific forms, might explain the tissue‐ specific processing of precursors.
Isolation and structure of pro-somatostatin: a putative somatostatin precursor from pig hypothalamus.
  • A. Schally, W. Huang, +5 authors L. Hood
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1980
TLDR
An octacosapeptide that is most likely a precursor (pro-hormone) of somatostatin in the hypothalamus has been isolated from acid extracts of porcine hypothalami and found to have the amino acid sequence Ser-Ala-Asn-Ser- asn-Pro- Ala-Met-AlA-Pro, which crossreacts strongly with antisera generated against the som atostatin tetradecapeptide.
Nonsomatostatin secretory peptide(s) derived from prosomatostatin's amino terminus in a rat medullary thyroid carcinoma cell line.
TLDR
A RIA for the amino terminus of proSS (proSS-NTP) is developed and demonstrated in acidic cell extracts two major proSS-nTP-containing species of 8000 and 4000 daltons, indicating that the 4000-dalton proSS/NTP species is not secreted.
...
1
2
3
4
...