Abstract
Neuroendocrine peptides mature partly through endoproteolytic processing of long precursor forms. Best characterised is cleavage at mono- and dibasic residues, but additional sites also exist. Among these is post-Phe cleavage, first suggested to participate in the processing of chicken progastrin. In order to characterise this new mechanism, antibodies recognising the processing products of post-Phe cleavage of chicken progastrin were produced for radioimmunoassay measurements and immunocytochemistry. High concentrations of the carboxyamidated C-terminus and the N-terminus of gastrin-53 were measured in extracts of the antrum. In addition, significant amounts were detected using an assay specific for the N-terminus of gastrin-30 and with another assay for the C-terminus of the corresponding peptide, gastrin-53(1-23), obtained after cleavage at the Phe(23)-Ala(24) bond of gastrin-53. Colocalisation in antral G-cells of the N-termini of gastrin-53 and gastrin-30 and of the C-terminus of gastrin-53(1-23) was confirmed by immunohistochemistry. Finally, we identified the intact N-terminal 1-23 fragment of gastrin-53 complementary to gastrin-30, verifying endoproteolytic cleavage at the Phe(23)-Ala(24) bond. Taken together, the results support the existence of vertebrate endoprotease cleaving hormone precursors at post-Phe sites.
| Original language | English |
|---|---|
| Journal | B B A - Reviews on Cancer |
| Volume | 1547 |
| Issue number | 1 |
| Pages (from-to) | 64-71 |
| Number of pages | 8 |
| ISSN | 0006-3002 |
| Publication status | Published - 5 May 2001 |
Keywords
- Amino Acid Sequence
- Animals
- Antibodies/immunology
- Binding Sites
- Chickens
- Chromatography, Gel
- Digestive System/metabolism
- Epitopes/immunology
- Fluorescent Antibody Technique
- Gastric Mucosa/metabolism
- Gastrins/chemistry
- Molecular Sequence Data
- Peptides/chemical synthesis
- Protein Precursors/chemistry
- Pyloric Antrum/metabolism
- Radioimmunoassay
- Tissue Extracts/chemistry