Abstract |
Among the members of the proprotein convertase (PC) family, PC1 and PC2 have well established roles as prohormone convertases. Another good candidate for this role is PC5-A that has been shown to be present in the regulated secretory pathway of certain neuroendocrine tissues, but evidence that it can process prohormones is lacking. To determine whether PC5-A could function as a prohormone convertase and to compare its cleavage specificity with that of PC1 and PC2, we stably transfected the rat pheochromocytoma PC12 cell line with PC5-A and analyzed the biosynthesis and subcellular localization of the enzyme, as well as its ability to process pro- neurotensin/ neuromedin N (pro-NT/NN) into active peptides. Our data showed that in transfected PC12 cells, PC5-A was converted from its 126-kDa precursor form into a 117-kDa mature form and, to a lesser extent, into a C-terminally truncated 65-kDa form of the 117-kDa product. Metabolic and immunochemical studies showed that PC5-A was sorted to early compartments of the regulated secretory pathway where it colocalized with immunoreactive NT. Furthermore, pro-NT/NN was processed in these compartments according to a pattern that differed from that previously described in PC1- and PC2-transfected PC12 cells. This pattern resembled that previously reported for pro-NT/NN processing in the adrenal medulla, a tissue known to express high levels of PC5-A. Altogether, these data demonstrate for the first time the ability of PC5-A to function as a prohormone convertase in the regulated secretory pathway and suggest a role for this enzyme in the physiological processing of pro-NT/NN.
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Authors | P Barbero, C Rovère, I De Bie, N Seidah, A Beaudet, P Kitabgi |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 273
Issue 39
Pg. 25339-46
(Sep 25 1998)
ISSN: 0021-9258 [Print] United States |
PMID | 9738000
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Protein Precursors
- Neurotensin
- Proprotein Convertase 5
- Serine Endopeptidases
- propeptide convertase 5, rat
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Topics |
- Amino Acid Sequence
- Amino Acid Substitution
- Animals
- Molecular Sequence Data
- Neurotensin
(metabolism)
- PC12 Cells
- Proprotein Convertase 5
- Protein Precursors
(metabolism)
- Protein Processing, Post-Translational
- Rats
- Serine Endopeptidases
(chemistry, genetics, metabolism)
- Transfection
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