Startseite Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs)
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Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs)

  • Katerina Oikonomopoulou , Kristina K. Hansen , Mahmoud Saifeddine , Nathalie Vergnolle , Illa Tea , Michael Blaber , Sachiko I. Blaber , Isobel Scarisbrick , Eleftherios P. Diamandis und Morley D. Hollenberg
Veröffentlicht/Copyright: 26. Juni 2006
Biological Chemistry
Aus der Zeitschrift Band 387 Heft 6

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.

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References

al-Ani, B., Saifeddine., M., and Hollenberg, M.D. (1995). Detection of functional receptors for the proteinase-activated-receptor-2-activating polypeptide, SLIGRL-NH2, in rat vascular and gastric smooth muscle. Can. J. Physiol. Pharmacol.73, 1203–1207.10.1139/y95-172Suche in Google Scholar

al-Ani, B., Saifeddine, M., Wijesuriya, S.J., and Hollenberg, M.D. (2002). Modified proteinase-activated receptor-1 and -2 derived peptides inhibit proteinase-activated receptor-2 activation by trypsin. J. Pharmacol. Exp. Ther.300, 702–708.10.1124/jpet.300.2.702Suche in Google Scholar

Blaber, S.I., Scarisbrick, I.A., Bernett, M.J., Dhanarajan, P., Seavy, M.A., Jin, Y., Schwartz, M.A., Rodriguez, M., and Blaber, M. (2002). Enzymatic properties of rat myelencephalon-specific protease. Biochemistry41, 1165–1173.10.1021/bi015781aSuche in Google Scholar

Borgono, C.A. and Diamandis, E.P. (2004). The emerging roles of human tissue kallikreins in cancer. Nat. Rev. Cancer4, 876–890.10.1038/nrc1474Suche in Google Scholar

Borgono, C.A., Grass, L., Soosaipillai, A., Yousef, G.M., Petraki, C.D., Howarth, D.H., Fracchioli, S., Katsaros, D., and Diamandis, E.P. (2003). Human kallikrein 14: a new potential biomarker for ovarian and breast cancer. Cancer Res.63, 9032–9041.Suche in Google Scholar

Borgono, C.A., Michael, I.P., and Diamandis, E.P. (2004). Human tissue kallikreins: physiologic roles and applications in cancer. Mol. Cancer Res.2, 257–280.10.1158/1541-7786.257.2.5Suche in Google Scholar

Cenac, N., Coelho, A.M., Nguyen, C., Compton, S., Andrade-Gordon, P., MacNaughton, W.K., Wallace, J.L., Hollenberg, M.D., Bunnett, N.W., Garcia-Villar, R., et al. (2002). Induction of intestinal inflammation in mouse by activation of proteinase-activated receptor-2. Am. J. Pathol.161, 1903–1915.10.1016/S0002-9440(10)64466-5Suche in Google Scholar

Choong, P.F. and Nadesapillai, A.P. (2003). Urokinase plasminogen activator system: a multifunctional role in tumor progression and metastasis. Clin. Orthop. Relat. Res.415, S46–58.10.1097/01.blo0000093845.72468.bdSuche in Google Scholar

Compton, S.J., McGuire, J.J., Saifeddine, M., and Hollenberg, M.D. (2002a). Restricted ability of human mast cell tryptase to activate proteinase-activated receptor-2 in rat aorta. Can. J. Physiol. Pharmacol.80, 987–992.10.1139/y02-125Suche in Google Scholar PubMed

Compton, S.J., Sandhu, S., Wijesuriya, S.J., and Hollenberg, M.D. (2002b). Glycosylation of human proteinase-activated receptor-2 (hPAR2): role in cell surface expression and signalling. Biochem. J.368, 495–505.10.1042/bj20020706Suche in Google Scholar

Corvera, C.U., Dery, O., McConalogue, K., Gamp, P., Thoma, M., al-Ani, B., Caughey, G.H., Hollenberg, M.D., and Bunnett, N.W. (1999). Thrombin and mast cell tryptase regulate guinea-pig myenteric neurons through proteinase-activated receptors-1 and -2. J. Physiol.517, 741–756.10.1111/j.1469-7793.1999.0741s.xSuche in Google Scholar PubMed PubMed Central

Coughlin, S.R. (2000). Thrombin signalling and protease-activated receptors. Nature407, 258–264.10.1038/35025229Suche in Google Scholar

Diamandis, E.P., Yousef, G.M., Soosaipillai, A.R., and Bunting, P. (2000). Human kallikrein 6 (zyme/protease M/neurosin): a new serum biomarker of ovarian carcinoma. Clin. Biochem.33, 579–583.10.1016/S0009-9120(00)00182-XSuche in Google Scholar

Frenette, G., Tremblay, R.R., Lazure, C., and Dube, J.Y. (1997). Prostatic kallikrein hK2, but not prostate-specific antigen (hK3), activates single-chain urokinase-type plasminogen activator. Int. J. Cancer71, 897–899.10.1002/(SICI)1097-0215(19970529)71:5<897::AID-IJC31>3.0.CO;2-2Suche in Google Scholar

Hollenberg, M.D. and Compton, S.J. (2002). International Union of Pharmacology. XXVIII. Proteinase-activated receptors. Pharmacol. Rev.54, 203–217.Suche in Google Scholar

Hollenberg, M.D. and Saifeddine, M. (2001). Proteinase-activated receptor 4 (PAR4): activation and inhibition of rat platelet aggregation by PAR4-derived peptides. Can. J. Physiol. Pharmacol.79, 439–442.10.1139/y01-013Suche in Google Scholar

Hollenberg, M.D., Laniyonu, A.A., Saifeddine, M., and Moore, G.J. (1993). Role of the amino- and carboxyl-terminal domains of thrombin receptor-derived polypeptides in biological activity in vascular endothelium and gastric smooth muscle: evidence for receptor subtypes. Mol. Pharmacol.43, 921–930.Suche in Google Scholar

Hollenberg, M.D., Saifeddine, M., and al-Ani, B. (1996). Proteinase-activated receptor-2 in rat aorta: structural requirements for agonist activity of receptor-activating peptides. Mol. Pharmacol.49, 229–233.Suche in Google Scholar

Hollenberg, M.D., Saifeddine, M., al-Ani, B., and Kawabata, A. (1997). Proteinase-activated receptors: structural requirements for activity, receptor cross-reactivity, and receptor selectivity of receptor-activating peptides. Can. J. Physiol. Pharmacol.75, 832–841.10.1139/y97-110Suche in Google Scholar

Hollenberg, M.D., Saifeddine, M., Sandhu, S., Houle, S., and Vergnolle, N. (2004). Proteinase-activated receptor-4: evaluation of tethered ligand-derived peptides as probes for receptor function and as inflammatory agonists in vivo. Br. J. Pharmacol.143, 443–454.10.1038/sj.bjp.0705946Suche in Google Scholar

Kawabata, A., Saifeddine, M., al-Ani, B., Leblond, L., and Hollenberg, M.D. (1999). Evaluation of proteinase-activated receptor-1 (PAR1). agonists and antagonists using a cultured cell receptor desensitization assay: activation of PAR2 by PAR1-targeted ligands. J. Pharmacol. Exp. Ther.288, 358–370.Suche in Google Scholar

Kim, H., Scorilas, A., Katsaros, D., Yousef, G.M., Massobrio, M., Fracchioli, S., Piccinno, R., Gordini, G., and Diamandis, E.P. (2001). Human kallikrein gene 5 (KLK5) expression is an indicator of poor prognosis in ovarian cancer. Br. J. Cancer84, 643–650.10.1054/bjoc.2000.1649Suche in Google Scholar

Kong, W., McConalogue, K., Khitin, L.M., Hollenberg, M.D., Payan, D.G., Bohm, S.K., and Bunnett, N.W. (1997). Luminal trypsin may regulate enterocytes through proteinase-activated receptor 2. Proc. Natl. Acad. Sci. USA94, 8884–8889.10.1073/pnas.94.16.8884Suche in Google Scholar

Macfarlane, S.R., Seatter, M.J., Kanke, T., Hunter, G.D., and Plevin, R. (2001). Proteinase-activated receptors. Pharmacol. Rev.53, 245–282.Suche in Google Scholar

Mirza, H., Schmidt, V.A., Derian, C.K., Jesty, J., and Bahou, W.F. (1997). Mitogenic responses mediated through the proteinase-activated receptor-2 are induced by expressed forms of mast cell α- or β-tryptases. Blood90, 3914–3922.10.1182/blood.V90.10.3914Suche in Google Scholar

Molino, M., Barnathan, E.S., Numerof, R., Clark, J., Dreyer, M., Cumashi, A., Hoxie, J.A., Schechter, N., Woolkalis, M., and Brass, L.F. (1997). Interactions of mast cell tryptase with thrombin receptors and PAR-2. J. Biol. Chem.272, 4043–4049.10.1074/jbc.272.7.4043Suche in Google Scholar

Nguyen, C., Coelho, A.M., Grady, E., Compton, S.J., Wallace, J.L., Hollenberg, M.D., Cenac, N., Garcia-Villar, R., Bueno, L., Steinhoff, M., et al. (2003). Colitis induced by proteinase-activated receptor-2 agonists is mediated by a neurogenic mechanism. Can. J. Physiol. Pharmacol.81, 920–927.10.1139/y03-080Suche in Google Scholar

Noorbakhsh, F., Vergnolle, N., Hollenberg, M.D., and Power, C. (2003). Proteinase-activated receptors in the nervous system. Nat. Rev. Neurosci.4, 981–990.10.1038/nrn1255Suche in Google Scholar

Noorbakhsh, F., Vergnolle, N., McArthur, J.C., Silva, C., Vodjgani, M., Andrade-Gordon, P., Hollenberg, M.D., and Power, C. (2005). Proteinase-activated receptor-2 induction by neuroinflammation prevents neuronal death during HIV infection. J. Immunol.174, 7320–7329.10.4049/jimmunol.174.11.7320Suche in Google Scholar

Nystedt, S., Emilsson, K., Wahlestedt, C., and Sundelin, J. (1994). Molecular cloning of a potential proteinase activated receptor. Proc. Natl. Acad. Sci. USA91, 9208–9212.10.1073/pnas.91.20.9208Suche in Google Scholar

Ossovskaya, V.S. and Bunnett, N.W. (2004). Protease-activated receptors: contribution to physiology and disease. Physiol. Rev.84, 579–621.10.1152/physrev.00028.2003Suche in Google Scholar

Rasmussen, U.B., Vouret-Craviari, V., Jallat, S., Schlesinger, Y., Pages, G., Pavirani, A., Lecocq, J.P., Pouyssegur, J., and Van Obberghen-Schilling, E. (1991). cDNA cloning and expression of a hamster alpha-thrombin receptor coupled to Ca2+ mobilization. FEBS Lett.288, 123–128.10.1016/0014-5793(91)81017-3Suche in Google Scholar

Ruf, W., Dorfleutner, A., and Riewald, M. (2003). Specificity of coagulation factor signaling. J. Thromb. Haemost.1, 1495–1503.10.1046/j.1538-7836.2003.00300.xSuche in Google Scholar PubMed

Saifeddine, M., al-Ani, B., Cheng, C.H., Wang, L., and Hollenberg, M.D. (1996). Rat proteinase-activated receptor-2 (PAR-2): cDNA sequence and activity of receptor-derived peptides in gastric and vascular tissue. Br. J. Pharmacol.118, 521–530.10.1111/j.1476-5381.1996.tb15433.xSuche in Google Scholar PubMed PubMed Central

Scarisbrick, I.A., Blaber, S.I., Lucchinetti, C.F., Genain, C.P., Blaber, M., and Rodriguez, M. (2002). Activity of a newly identified serine protease in CNS demyelination. Brain125, 1283–1296.10.1093/brain/awf142Suche in Google Scholar PubMed

Steinhoff, M., Buddenkotte, J., Shpacovitch, V., Rattenholl, A., Moormann, C., Vergnolle, N., Luger, T.A., and Hollenberg, M.D. (2005). Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response. Endocr. Rev.26, 1–43.10.1210/er.2003-0025Suche in Google Scholar PubMed

Takayama, T.K., McMullen, B.A., Nelson, P.S., Matsumura, M., and Fujikawa, K. (2001). Characterization of hK4 (prostase), a prostate-specific serine protease: activation of the precursor of prostate specific antigen (pro-PSA) and single-chain urokinase-type plasminogen activator and degradation of prostatic acid phosphatase. Biochemistry40, 15341–15348.10.1021/bi015775eSuche in Google Scholar

Tanimoto, H., Underwood, L.J., Shigemasa, K., Parmley, T.H., and O'Brien, T.J. (2001). Increased expression of protease M in ovarian tumors. Tumour Biol.22, 11–18.10.1159/000030150Suche in Google Scholar

Vergnolle, N. (2004). Modulation of visceral pain and inflammation by protease-activated receptors. Br. J. Pharmacol.141, 1264–1274.10.1038/sj.bjp.0705750Suche in Google Scholar

Vergnolle, N. (2005). Clinical relevance of proteinase activated receptors (PARs) in the gut. Gut54, 867–874.10.1136/gut.2004.048876Suche in Google Scholar

Vergnolle, N., Hollenberg, M.D., and Wallace, J.L. (1999a). Pro- and anti-inflammatory actions of thrombin: a distinct role for proteinase-activated receptor-1 (PAR1). Br. J. Pharmacol.126, 1262–1268.10.1038/sj.bjp.0702408Suche in Google Scholar

Vergnolle, N., Hollenberg, M.D., Sharkey, K.A., and Wallace, J.L. (1999b). Characterization of the inflammatory response to proteinase-activated receptor-2 (PAR2)-activating peptides in the rat paw. Br. J. Pharmacol.127, 1083–1090.10.1038/sj.bjp.0702634Suche in Google Scholar

Vergnolle, N., Bunnett, N.W., Sharkey, K.A., Brussee, V., Compton, S.J., Grady, E.F., Cirino, G., Gerard, N., Basbaum, A.I., Andrade-Gordon, P., Hollenberg, M.D., and Wallace, J.L. (2001a). Proteinase-activated receptor-2 and hyperalgesia: a novel pain pathway. Nat. Med.7, 821–826.10.1038/89945Suche in Google Scholar

Vergnolle, N., Wallace, J.L., Bunnett, N.W., and Hollenberg, M.D. (2001b). Protease-activated receptors in inflammation, neuronal signaling and pain. Trends. Pharmacol. Sci.22, 146–152.10.1016/S0165-6147(00)01634-5Suche in Google Scholar

Vu, T.K., Hung, D.T., Wheaton, V.I., and Coughlin, S.R. (1991). Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell64, 1057–1068.10.1016/0092-8674(91)90261-VSuche in Google Scholar

Yousef, G.M., Polymeris, M.E., Grass, L., Soosaipillai, A., Chan, P.C., Scorilas, A., Borgono, C., Harbeck, N., Schmalfeldt, B., Dorn, J., et al. (2003). Human kallikrein 5, a potential novel serum biomarker for breast and ovarian cancer. Cancer Res.63, 3958–3965.Suche in Google Scholar

Published Online: 2006-06-26
Published in Print: 2006-06-01

©2006 by Walter de Gruyter Berlin New York

Artikel in diesem Heft

  1. The First International Symposium on Kallikreins
  2. A comprehensive nomenclature for serine proteases with homology to tissue kallikreins
  3. The kallikrein world: an update on the human tissue kallikreins
  4. Cellular distribution of human tissue kallikreins: immunohistochemical localization
  5. The tissue kallikrein-kinin system protects against cardiovascular and renal diseases and ischemic stroke independently of blood pressure reduction
  6. Proteinase-mediated cell signalling: targeting proteinase-activated receptors (PARs) by kallikreins and more
  7. Recombinant kallikrein expression: site-specific integration for hK6 production in human cells
  8. Kallikrein-related peptidase (KLK) family mRNA variants and protein isoforms in hormone-related cancers: do they have a function?
  9. The role of kallikrein-related peptidases in prostate cancer: potential involvement in an epithelial to mesenchymal transition
  10. Human kallikrein 10, a predictive marker for breast cancer
  11. Activation and enzymatic characterization of recombinant human kallikrein 8
  12. Human tissue kallikrein 9: production of recombinant proteins and specific antibodies
  13. The human kallikrein 10 promoter contains a functional retinoid response element
  14. Human kallikrein 4: enzymatic activity, inhibition, and degradation of extracellular matrix proteins
  15. Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum
  16. A sensitive proximity ligation assay for active PSA
  17. Multiple mechanisms underlie the aberrant expression of the human kallikrein 6 gene in breast cancer
  18. Expression of the human kallikrein genes 10 (KLK10) and 11 (KLK11) in cancerous and non-cancerous lung tissues
  19. 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
  20. The epigenetic basis for the aberrant expression of kallikreins in human cancers
  21. Improved prostate cancer detection with a human kallikrein 11 and percentage free PSA-based artificial neural network
  22. Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases the malignant phenotype of ovarian cancer cells
  23. Inhibition profiles of human tissue kallikreins by serine protease inhibitors
  24. Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs)
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