| Title | Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancer. | | Author(s) | Hollenberg MD, Oikonomopoulou K, Hansen KK, Saifeddine M, Ramachandran R, Diamandis EP | | Institution | Proteinases and Inflammation Network, Department of Pharmacology and Therapeutics, University of Calgary Faculty of Medicine, Calgary T2N 4N1, AB, Canada. | | Source | Biol Chem 2008 Jun 20. | | Abstract | Abstract Proteinases like thrombin and trypsin can affect tissues by activating a novel family of G-protein-coupled Proteinase-Activated Receptors (PARs 1 to 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, lungs 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 dis-arming PARs, proteinases can also cause hormone-like effects by PAR-independent mechanisms, like 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 (KLK) 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18627296 |
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