Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs)
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Katerina Oikonomopoulou
Abstract
We tested the hypothesis that human tissue kallikreins (hKs) may regulate signal transduction by cleaving and activating proteinase-activated receptors (PARs). We found that hK5, 6 and 14 cleaved PAR N-terminal peptide sequences representing the cleavage/activation motifs of human PAR1 and PAR2 to yield receptor-activating peptides. hK5, 6 and 14 activated calcium signalling in rat PAR2-expressing (but not background) KNRK cells. Calcium signalling in HEK cells co-expressing human PAR1 and PAR2 was also triggered by hK14 (via PAR1 and PAR2) and hK6 (via PAR2). In isolated rat platelets that do not express PAR1, but signal via PAR4, hK14 also activated PAR-dependent calcium signalling responses and triggered aggregation. The aggregation response elicited by hK14 was in contrast to the lack of aggregation triggered by hK5 and 6. hK14 also caused vasorelaxation in a phenylephrine-preconstricted rat aorta ring assay and triggered oedema in an in vivo model of murine paw inflammation. We propose that, like thrombin and trypsin, the kallikreins must now be considered as important ‘hormonal’ regulators of tissue function, very likely acting in part via PARs.
References
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Artikel in diesem Heft
- The First International Symposium on Kallikreins
- A comprehensive nomenclature for serine proteases with homology to tissue kallikreins
- The kallikrein world: an update on the human tissue kallikreins
- Cellular distribution of human tissue kallikreins: immunohistochemical localization
- The tissue kallikrein-kinin system protects against cardiovascular and renal diseases and ischemic stroke independently of blood pressure reduction
- Proteinase-mediated cell signalling: targeting proteinase-activated receptors (PARs) by kallikreins and more
- Recombinant kallikrein expression: site-specific integration for hK6 production in human cells
- Kallikrein-related peptidase (KLK) family mRNA variants and protein isoforms in hormone-related cancers: do they have a function?
- The role of kallikrein-related peptidases in prostate cancer: potential involvement in an epithelial to mesenchymal transition
- Human kallikrein 10, a predictive marker for breast cancer
- Activation and enzymatic characterization of recombinant human kallikrein 8
- Human tissue kallikrein 9: production of recombinant proteins and specific antibodies
- The human kallikrein 10 promoter contains a functional retinoid response element
- Human kallikrein 4: enzymatic activity, inhibition, and degradation of extracellular matrix proteins
- Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum
- A sensitive proximity ligation assay for active PSA
- Multiple mechanisms underlie the aberrant expression of the human kallikrein 6 gene in breast cancer
- Expression of the human kallikrein genes 10 (KLK10) and 11 (KLK11) in cancerous and non-cancerous lung tissues
- mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy
- The epigenetic basis for the aberrant expression of kallikreins in human cancers
- Improved prostate cancer detection with a human kallikrein 11 and percentage free PSA-based artificial neural network
- Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases the malignant phenotype of ovarian cancer cells
- Inhibition profiles of human tissue kallikreins by serine protease inhibitors
- Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs)
Artikel in diesem Heft
- The First International Symposium on Kallikreins
- A comprehensive nomenclature for serine proteases with homology to tissue kallikreins
- The kallikrein world: an update on the human tissue kallikreins
- Cellular distribution of human tissue kallikreins: immunohistochemical localization
- The tissue kallikrein-kinin system protects against cardiovascular and renal diseases and ischemic stroke independently of blood pressure reduction
- Proteinase-mediated cell signalling: targeting proteinase-activated receptors (PARs) by kallikreins and more
- Recombinant kallikrein expression: site-specific integration for hK6 production in human cells
- Kallikrein-related peptidase (KLK) family mRNA variants and protein isoforms in hormone-related cancers: do they have a function?
- The role of kallikrein-related peptidases in prostate cancer: potential involvement in an epithelial to mesenchymal transition
- Human kallikrein 10, a predictive marker for breast cancer
- Activation and enzymatic characterization of recombinant human kallikrein 8
- Human tissue kallikrein 9: production of recombinant proteins and specific antibodies
- The human kallikrein 10 promoter contains a functional retinoid response element
- Human kallikrein 4: enzymatic activity, inhibition, and degradation of extracellular matrix proteins
- Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum
- A sensitive proximity ligation assay for active PSA
- Multiple mechanisms underlie the aberrant expression of the human kallikrein 6 gene in breast cancer
- Expression of the human kallikrein genes 10 (KLK10) and 11 (KLK11) in cancerous and non-cancerous lung tissues
- mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy
- The epigenetic basis for the aberrant expression of kallikreins in human cancers
- Improved prostate cancer detection with a human kallikrein 11 and percentage free PSA-based artificial neural network
- Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases the malignant phenotype of ovarian cancer cells
- Inhibition profiles of human tissue kallikreins by serine protease inhibitors
- Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs)