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Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancer.
Biol Chem. 2008 Jun; 389(6):643-51.BC

Abstract

Proteinases such as thrombin and trypsin can affect tissues by activating a novel family of G protein-coupled proteinase-activated receptors (PARs 1-4) by exposing a 'tethered' receptor-triggering ligand (TL). Work with synthetic TL-derived PAR peptide sequences (PAR-APs) that stimulate PARs 1, 2 and 4 has shown that PAR activation can play a role in many tissues, including the gastrointestinal tract, kidney, muscle, nerve, lung and the central and peripheral nervous systems, and can promote tumor growth and invasion. PARs may play roles in many settings, including cancer, arthritis, asthma, inflammatory bowel disease, neurodegeneration and cardiovascular disease, as well as in pathogen-induced inflammation. In addition to activating or disarming PARs, proteinases can also cause hormone-like effects via PAR-independent mechanisms, such as activation of the insulin receptor. In addition to proteinases of the coagulation cascade, recent data suggest that members of the family of kallikrein-related peptidases (KLKs) represent endogenous PAR regulators. In summary: (1) proteinases are like hormones, signaling in a paracrine and endocrine manner via PARs or other mechanisms; (2) KLKs must now be seen as potential hormone-like PAR regulators in vivo; and (3) PAR-regulating proteinases, their target PARs, and their associated signaling pathways appear to be novel therapeutic targets.

Authors+Show Affiliations

Proteinases and Inflammation Network, Department of Pharmacology and Therapeutics, University of Calgary Faculty of Medicine, Calgary T2N 4N1, AB, Canada. mhollenb@ucalgary.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

18627296

Citation

Hollenberg, Morley D., et al. "Kallikreins and Proteinase-mediated Signaling: Proteinase-activated Receptors (PARs) and the Pathophysiology of Inflammatory Diseases and Cancer." Biological Chemistry, vol. 389, no. 6, 2008, pp. 643-51.
Hollenberg MD, Oikonomopoulou K, Hansen KK, et al. Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancer. Biol Chem. 2008;389(6):643-51.
Hollenberg, M. D., Oikonomopoulou, K., Hansen, K. K., Saifeddine, M., Ramachandran, R., & Diamandis, E. P. (2008). Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancer. Biological Chemistry, 389(6), 643-51. https://doi.org/10.1515/BC.2008.077
Hollenberg MD, et al. Kallikreins and Proteinase-mediated Signaling: Proteinase-activated Receptors (PARs) and the Pathophysiology of Inflammatory Diseases and Cancer. Biol Chem. 2008;389(6):643-51. PubMed PMID: 18627296.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancer. AU - Hollenberg,Morley D, AU - Oikonomopoulou,Katerina, AU - Hansen,Kristina K, AU - Saifeddine,Mahmoud, AU - Ramachandran,Rithwik, AU - Diamandis,Eleftherios P, PY - 2008/7/17/pubmed PY - 2008/9/27/medline PY - 2008/7/17/entrez SP - 643 EP - 51 JF - Biological chemistry JO - Biol Chem VL - 389 IS - 6 N2 - Proteinases such as thrombin and trypsin can affect tissues by activating a novel family of G protein-coupled proteinase-activated receptors (PARs 1-4) by exposing a 'tethered' receptor-triggering ligand (TL). Work with synthetic TL-derived PAR peptide sequences (PAR-APs) that stimulate PARs 1, 2 and 4 has shown that PAR activation can play a role in many tissues, including the gastrointestinal tract, kidney, muscle, nerve, lung and the central and peripheral nervous systems, and can promote tumor growth and invasion. PARs may play roles in many settings, including cancer, arthritis, asthma, inflammatory bowel disease, neurodegeneration and cardiovascular disease, as well as in pathogen-induced inflammation. In addition to activating or disarming PARs, proteinases can also cause hormone-like effects via PAR-independent mechanisms, such as activation of the insulin receptor. In addition to proteinases of the coagulation cascade, recent data suggest that members of the family of kallikrein-related peptidases (KLKs) represent endogenous PAR regulators. In summary: (1) proteinases are like hormones, signaling in a paracrine and endocrine manner via PARs or other mechanisms; (2) KLKs must now be seen as potential hormone-like PAR regulators in vivo; and (3) PAR-regulating proteinases, their target PARs, and their associated signaling pathways appear to be novel therapeutic targets. SN - 1431-6730 UR - https://www.unboundmedicine.com/medline/citation/18627296/Kallikreins_and_proteinase_mediated_signaling:_proteinase_activated_receptors__PARs__and_the_pathophysiology_of_inflammatory_diseases_and_cancer_ L2 - https://www.degruyter.com/document/doi/10.1515/BC.2008.077 DB - PRIME DP - Unbound Medicine ER -