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Interaction of Protein C Inhibitor with the Type II Transmembrane Serine Protease Enteropeptidase

The serine protease inhibitor protein C inhibitor (PCI) is expressed in many human tissues and exhibits broad protease reactivity. PCI binds glycosaminoglycans and certain phospholipids, which modulate its inhibitory activity. Enteropeptidase (EP) is a type II transmembrane serine protease mainly fo...

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Autores principales: Prohaska, Thomas A., Wahlmüller, Felix C., Furtmüller, Margareta, Geiger, Margarethe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378520/
https://www.ncbi.nlm.nih.gov/pubmed/22723979
http://dx.doi.org/10.1371/journal.pone.0039262
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author Prohaska, Thomas A.
Wahlmüller, Felix C.
Furtmüller, Margareta
Geiger, Margarethe
author_facet Prohaska, Thomas A.
Wahlmüller, Felix C.
Furtmüller, Margareta
Geiger, Margarethe
author_sort Prohaska, Thomas A.
collection PubMed
description The serine protease inhibitor protein C inhibitor (PCI) is expressed in many human tissues and exhibits broad protease reactivity. PCI binds glycosaminoglycans and certain phospholipids, which modulate its inhibitory activity. Enteropeptidase (EP) is a type II transmembrane serine protease mainly found on the brush border membrane of epithelial cells in the duodenum, where it activates trypsinogen to initiate the digestion of food proteins. Some active EP is also present in duodenal fluid and has been made responsible for causing pancreatitis in case of duodeno-pancreatic reflux. Together with its substrate trypsinogen, EP is furthermore present in the epidermis and in some cancer cells. In this report, we show that PCI inhibited EP with an apparent 2nd order rate constant of 4.48×10(4) M(−1) s(−1). Low molecular weight (LMWH) and unfractionated heparin (UFH) slightly reduced the inhibitory effect of PCI. The SI (stoichiometry of inhibition) value for the inhibition of EP by PCI was 10.8 in the absence and 17.9 in the presence of UFH (10 U/ml). By inhibiting trypsin, chymotrypsin, and additionally EP, PCI might play a role in the protection of the pancreas from autodigestion. Furthermore the interaction of PCI with EP may influence the regulation of epithelial differentiation.
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spelling pubmed-33785202012-06-21 Interaction of Protein C Inhibitor with the Type II Transmembrane Serine Protease Enteropeptidase Prohaska, Thomas A. Wahlmüller, Felix C. Furtmüller, Margareta Geiger, Margarethe PLoS One Research Article The serine protease inhibitor protein C inhibitor (PCI) is expressed in many human tissues and exhibits broad protease reactivity. PCI binds glycosaminoglycans and certain phospholipids, which modulate its inhibitory activity. Enteropeptidase (EP) is a type II transmembrane serine protease mainly found on the brush border membrane of epithelial cells in the duodenum, where it activates trypsinogen to initiate the digestion of food proteins. Some active EP is also present in duodenal fluid and has been made responsible for causing pancreatitis in case of duodeno-pancreatic reflux. Together with its substrate trypsinogen, EP is furthermore present in the epidermis and in some cancer cells. In this report, we show that PCI inhibited EP with an apparent 2nd order rate constant of 4.48×10(4) M(−1) s(−1). Low molecular weight (LMWH) and unfractionated heparin (UFH) slightly reduced the inhibitory effect of PCI. The SI (stoichiometry of inhibition) value for the inhibition of EP by PCI was 10.8 in the absence and 17.9 in the presence of UFH (10 U/ml). By inhibiting trypsin, chymotrypsin, and additionally EP, PCI might play a role in the protection of the pancreas from autodigestion. Furthermore the interaction of PCI with EP may influence the regulation of epithelial differentiation. Public Library of Science 2012-06-19 /pmc/articles/PMC3378520/ /pubmed/22723979 http://dx.doi.org/10.1371/journal.pone.0039262 Text en Prohaska et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Prohaska, Thomas A.
Wahlmüller, Felix C.
Furtmüller, Margareta
Geiger, Margarethe
Interaction of Protein C Inhibitor with the Type II Transmembrane Serine Protease Enteropeptidase
title Interaction of Protein C Inhibitor with the Type II Transmembrane Serine Protease Enteropeptidase
title_full Interaction of Protein C Inhibitor with the Type II Transmembrane Serine Protease Enteropeptidase
title_fullStr Interaction of Protein C Inhibitor with the Type II Transmembrane Serine Protease Enteropeptidase
title_full_unstemmed Interaction of Protein C Inhibitor with the Type II Transmembrane Serine Protease Enteropeptidase
title_short Interaction of Protein C Inhibitor with the Type II Transmembrane Serine Protease Enteropeptidase
title_sort interaction of protein c inhibitor with the type ii transmembrane serine protease enteropeptidase
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378520/
https://www.ncbi.nlm.nih.gov/pubmed/22723979
http://dx.doi.org/10.1371/journal.pone.0039262
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