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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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IMPACT FACTOR 2015: 2.710
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Online
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1437-4315
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Volume 389, Issue 8 (Aug 2008)

Issues

Proteinases as hormones: targets and mechanisms for proteolytic signaling

Kristina K. Hansen
  • 1Proteinases and Inflammation Network, University of Calgary Faculty of Medicine, Calgary T2N 4N1, AB, Canada
/ Katerina Oikonomopoulou
  • 2Advanced Center for Detection of Cancer, Mount Sinai Hospital and University of Toronto, Toronto M5T 3L9, ON, Canada
/ Amos Baruch
  • 3KAI Pharmaceuticals, South San Francisco, CA 94080, USA
/ Rithwik Ramachandran
  • 4Proteinases and Inflammation Network, University of Calgary Faculty of Medicine, Calgary T2N 4N1, AB, Canada
/ Paul Beck
  • 5Proteinases and Inflammation Network, University of Calgary Faculty of Medicine, Calgary T2N 4N1, AB, Canada
/ Eleftherios P. Diamandis
  • 6Advanced Center for Detection of Cancer, Mount Sinai Hospital and University of Toronto, Toronto M5T 3L9, ON, Canada
/ Morley D. Hollenberg
  • 7Proteinases and Inflammation Network, University of Calgary Faculty of Medicine, Calgary T2N 4N1, AB, Canada
Published Online: 2008-08-19 | DOI: https://doi.org/10.1515/BC.2008.120

Abstract

Proteinases, such as kallikrein-related peptidases, trypsin and thrombin, can play hormone-like ‘messenger’ roles in vivo. They can regulate cell signaling by cleaving and activating a novel family of G-protein-coupled proteinase-activated receptors (PARs 1–4) by unmasking a tethered receptor-triggering ligand. Short synthetic PAR-derived peptide sequences (PAR-APs) can selectively activate PARs 1, 2 and 4, causing physiological responses in vitro and in vivo. Using the PAR-APs to activate the receptors in vivo, it has been found that PARs, like hormone receptors, can affect the vascular, renal, respiratory, gastrointestinal, musculoskeletal and nervous systems (central and peripheral). PARs trigger responses ranging from vasodilatation to intestinal inflammation, increased cytokine production and increased nociception. These PAR-stimulated responses have been implicated in various disease states, including cancer, atherosclerosis, asthma, arthritis, colitis and Alzheimer's disease. In addition to targeting the PARs, proteinases can also cause hormone-like effects by other signaling mechanisms that may be as important as the activation of PARs. Thus, the PARs themselves, their activating serine proteinases and their signaling pathways can be considered as attractive targets for therapeutic drug development. Further, proteinases can be considered as physiologically relevant ‘hormone-like’ messengers that can convey signals locally or systemically either via PARs or by other mechanisms.

Keywords: activity-based probes; coagulation; kallikrein-related peptidases; proteinase; proteinase-activated receptors; thrombin

About the article

Corresponding author


Published Online: 2008-08-19

Published in Print: 2008-08-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2008.120. Export Citation

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