Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancer
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Morley D. Hollenberg
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.
©2008 by Walter de Gruyter Berlin New York
Artikel in diesem Heft
- Editorial
- Kallikreins and kallikrein-related peptidases
- Guest Editorial
- The 2nd International Symposium on Kallikreins and Kallikrein-Related Peptidases (ISK 2007) and the Commemorative Gold Medal of the E.K. Frey–E. Werle Foundation of the Henning L. Voigt Family
- Highlight: Kallikrein, kinins and kallikrein-related peptidases
- Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7
- Development of peptides specifically modulating the activity of KLK2 and KLK3
- Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancer
- Prostatic trypsin-like kallikrein-related peptidases (KLKs) and other prostate-expressed tryptic proteinases as regulators of signalling via proteinase-activated receptors (PARs)
- Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier functions
- A potential role for tissue kallikrein-related peptidases in human cervico-vaginal physiology
- microRNAs: a new frontier in kallikrein research
- Functions of KLK4 and MMP-20 in dental enamel formation
- Genetic deficiency in tissue kallikrein activity in mouse and man: effect on arteries, heart and kidney
- Development of diabetic cardiomyopathy and the kallikrein-kinin system – new insights from B1 and B2 receptor signaling
- Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor
- Attenuation of left ventricular dysfunction by an ACE inhibitor after myocardial infarction in a kininogen-deficient rat model
- Tissue kallikrein and kinin infusion promotes neovascularization in limb ischemia
- Kallikreins as microRNA targets: an in silico and experimental-based analysis
- Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration
- Immunofluorometric activity-based probe analysis of active KLK6 in biological fluids
- Kallikrein 6 is a mediator of K-RAS-dependent migration of colon carcinoma cells
- Gene expression changes associated with the anti-angiogenic activity of kallikrein-related peptidase 3 (KLK3) on human umbilical vein endothelial cells
- An AKT activity threshold regulates androgen-dependent and androgen-independent PSA expression in prostate cancer cell lines
- Quantitative RT-PCR analysis and immunohistochemical localization of the kallikrein-related peptidases 13 and 14 in lung
Artikel in diesem Heft
- Editorial
- Kallikreins and kallikrein-related peptidases
- Guest Editorial
- The 2nd International Symposium on Kallikreins and Kallikrein-Related Peptidases (ISK 2007) and the Commemorative Gold Medal of the E.K. Frey–E. Werle Foundation of the Henning L. Voigt Family
- Highlight: Kallikrein, kinins and kallikrein-related peptidases
- Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7
- Development of peptides specifically modulating the activity of KLK2 and KLK3
- Kallikreins and proteinase-mediated signaling: proteinase-activated receptors (PARs) and the pathophysiology of inflammatory diseases and cancer
- Prostatic trypsin-like kallikrein-related peptidases (KLKs) and other prostate-expressed tryptic proteinases as regulators of signalling via proteinase-activated receptors (PARs)
- Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier functions
- A potential role for tissue kallikrein-related peptidases in human cervico-vaginal physiology
- microRNAs: a new frontier in kallikrein research
- Functions of KLK4 and MMP-20 in dental enamel formation
- Genetic deficiency in tissue kallikrein activity in mouse and man: effect on arteries, heart and kidney
- Development of diabetic cardiomyopathy and the kallikrein-kinin system – new insights from B1 and B2 receptor signaling
- Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor
- Attenuation of left ventricular dysfunction by an ACE inhibitor after myocardial infarction in a kininogen-deficient rat model
- Tissue kallikrein and kinin infusion promotes neovascularization in limb ischemia
- Kallikreins as microRNA targets: an in silico and experimental-based analysis
- Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration
- Immunofluorometric activity-based probe analysis of active KLK6 in biological fluids
- Kallikrein 6 is a mediator of K-RAS-dependent migration of colon carcinoma cells
- Gene expression changes associated with the anti-angiogenic activity of kallikrein-related peptidase 3 (KLK3) on human umbilical vein endothelial cells
- An AKT activity threshold regulates androgen-dependent and androgen-independent PSA expression in prostate cancer cell lines
- Quantitative RT-PCR analysis and immunohistochemical localization of the kallikrein-related peptidases 13 and 14 in lung
