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Cellular Peptide Hormone Synthesis and Secretory Pathways pp 63–84Cite as

Neurotensin and Neuromedin N Are Differentially Processed from a Common Precursor by Prohormone Convertases in Tissues and Cell Lines

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Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 50))

Abstract

Neurotensin (NT) is synthesized as part of a larger precursor that also contains neuromedin N (NN), a six amino acid NT-like peptide. NT and NN are located in the C-terminal region of the precursor (pro-NT/NN) where they are flanked and separated by three Lys–Arg sequences. A fourth dibasic sequence is present in the middle of the precursor. Dibasics are the consensus sites recognized and cleaved by specialized endoproteases that belong to the family of proprotein convertases (PCs). In tissues that express pro-NT/NN, the three C-terminal Lys–Arg sites are differentially processed, whereas the middle dibasic is poorly cleaved. Processing gives rise mainly to NT and NN in the brain, NT and a large peptide with a C-terminal NN moiety (large NN) in the gut, and NT, large NN, and a large peptide with a C-terminal NT moiety (large NT) in the adrenals. Recent evidence indicates that PC1, PC2, and PC5-A are the prohormone convertases responsible for the processing patterns observed in the gut, brain, and adrenals, respectively. As NT, NN, large NT, and large NN are all endowed with biological activity, the evidence reviewed here supports the idea that posttranslational processing of pro-NT/NN in tissues may generate biological diversity of pathophysiological relevance.

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Authors and Affiliations

  1. Inserm U938, Hopital St-Antoine, 184 rue du Faubourg St-Antoine, 75571, Paris CEDEX 12, France

    Patrick Kitabgi

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  1. Patrick Kitabgi
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Correspondence to Patrick Kitabgi .

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Editors and Affiliations

  1. Rigshospitalet, Koebenhavns Universitet, Blegdamsvej 9, Koebenhavn, 2100, Denmark

    Jens F. Rehfeld

  2. Rigshospitalet, Koebenhavns Universitet, Blegdamsvej 9, Koebenhavn OE, 2100, Denmark

    Jens R. Bundgaard

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Kitabgi, P. (2009). Neurotensin and Neuromedin N Are Differentially Processed from a Common Precursor by Prohormone Convertases in Tissues and Cell Lines. In: Rehfeld, J., Bundgaard, J. (eds) Cellular Peptide Hormone Synthesis and Secretory Pathways. Results and Problems in Cell Differentiation, vol 50. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2009_27

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