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Prostatic trypsin-like kallikrein-related peptidases (KLKs) and other prostate-expressed tryptic proteinases as regulators of signalling via proteinase-activated receptors (PARs)
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Andrew J. Ramsay
Published/Copyright:
May 15, 2008
Abstract
The prostate is a site of high expression of serine proteinases including members of the kallikrein-related peptidase (KLK) family, as well as other secreted and membrane-anchored serine proteinases. It has been known for some time that members of this enzyme family elicit cellular responses by acting directly on cells. More recently, it has been recognised that for serine proteinases with specificity for cleavage after arginine and lysine residues (trypsin-like or tryptic enzymes) these cellular responses are often mediated by cleavage of members of the proteinase-activated receptor (PAR) family – a four member sub-family of G protein-coupled receptors. Here, we review the expression of PARs in prostate, the ability of prostatic trypsin-like KLKs and other prostate-expressed tryptic enzymes to cleave PARs, as well as the prostate cancer-associated consequences of PAR activation. In addition, we explore the dysregulation of trypsin-like serine proteinase activity through the loss of normal inhibitory mechanisms and potential interactions between these dysregulated enzymes leading to aberrant PAR activation, intracellular signalling and cancer-promoting cellular changes.
Keywords: cancer; kallikrein-related peptidase; prostate; proteinase-activated receptor; serine proteinase
Published Online: 2008-05-15
Published in Print: 2008-06-01
©2008 by Walter de Gruyter Berlin New York
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Articles in the same Issue
- 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
Keywords for this article
cancer;
kallikrein-related peptidase;
prostate;
proteinase-activated receptor;
serine proteinase
Articles in the same Issue
- 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
