Home Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum
Article
Licensed
Unlicensed Requires Authentication

Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum

  • Kristina Stefansson , Maria Brattsand , Annelii Ny , Bo Glas and Torbjörn Egelrud
Published/Copyright: June 26, 2006
Biological Chemistry
From the journal Volume 387 Issue 6

Abstract

We have previously presented evidence that two human kallikrein-related peptidases, KLK5 (hK5, stratum corneum tryptic enzyme, SCTE) and KLK7 (hK7, stratum corneum chymotryptic enzyme, SCCE), which are abundant in the stratum corneum, may be involved in desquamation. Since we had noted that not all trypsin-like activity in the plantar stratum corneum could be ascribed to KLK5, we set out to identify other skin proteases with similar primary substrate specificity. Here we describe purification of a protease identified as KLK14 from plantar stratum corneum, and show that this enzyme may be responsible for as much as 50% of the total trypsin-like activity in this tissue, measured as activity towards a chromogenic substrate cleaved by a wide variety of enzymes with trypsin-like specificity. This was in spite of very low levels of KLK14 protein compared to KLK5 and KLK7. KLK14 could be detected by immunoblotting in normal superficial stratum corneum of all individuals examined. The majority of KLK14 in the plantar stratum corneum is present in its catalytically active form. KLK14 could be immunohistochemically detected in sweat ducts, preferentially in the intraepidermal parts (the acrosyringium), and in sweat glands. The role played by this very efficient protease under normal and disease conditions in the skin remains to be elucidated.

:

Corresponding author

References

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.Search in Google Scholar

Brattsand, M. and Egelrud, T. (1999). Purification, molecular cloning, and expression of a human stratum corneum trypsin-like serine protease with possible function in desquamation. J. Biol. Chem.274, 30033–30040.10.1074/jbc.274.42.30033Search in Google Scholar PubMed

Brattsand, M., Stefansson, K., Lundh, C., Haasum, Y., and Egelrud, T. (2005). A proteolytic cascade of kallikreins in the stratum corneum. J. Invest. Dermatol.124, 198–203.10.1111/j.0022-202X.2004.23547.xSearch in Google Scholar PubMed

Caubet, C., Jonca, N., Brattsand, M., Guerrin, M., Bernard, D., Schmidt, R., Egelrud, T., Simon, M., and Serre, G. (2004). Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7. J. Invest. Dermatol.122, 1235–1244.10.1111/j.0022-202X.2004.22512.xSearch in Google Scholar PubMed

Chao, S.C., Richard, G., and Lee, J.Y. (2005). Netherton syndrome: report of two Taiwanese siblings with staphylococcal scalded skin syndrome and mutation of SPINK5. Br. J. Dermatol.152, 159–165.10.1111/j.1365-2133.2005.06337.xSearch in Google Scholar PubMed

Chavanas, S., Bodemer, C., Rochat, A., Hamel-Teillac, D., Ali, M., Irvine, A.D., Bonafe, J.L., Wilkinson, J., Taieb, A., Barrandon, Y., et al. (2000). Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat. Genet.25, 141–142.10.1038/75977Search in Google Scholar PubMed

Clements, J., Hooper, J., Dong, Y., and Harvey, T. (2001). The expanded human kallikrein (KLK) gene family: genomic organisation, tissue-specific expression and potential functions. Biol. Chem.382, 5–14.10.1515/BC.2001.002Search in Google Scholar PubMed

Egelrud, T. (1993). Purification and preliminary characterization of stratum corneum chymotryptic enzyme: a proteinase that may be involved in desquamation. J. Invest. Dermatol.101, 200–204.10.1111/1523-1747.ep12363804Search in Google Scholar PubMed

Egelrud, T. (2000a). Desquamation in the stratum corneum. Acta Derm. Venereol. Suppl.208, 44–45.10.1080/000155500750042853Search in Google Scholar

Egelrud, T. (2000b). Desquamation. In: Dry Skin and Moisturizers, M. Lodén and H.I. Maibach, eds. (Washington, DC, USA: CRC Press), pp. 109–117.Search in Google Scholar

Egelrud, T. and Lundström, A. (1991). A chymotrypsin-like proteinase that may be involved in desquamation in plantar stratum corneum. Arch. Dermatol. Res.283, 108–112.10.1007/BF00371618Search in Google Scholar PubMed

Ekholm, E. and Egelrud, T. (1998). The expression of stratum corneum chymotryptic enzyme in human anagen hair follicles: further evidence for its involvement in desquamation-like processes. Br. J. Dermatol.139, 585–590.10.1046/j.1365-2133.1998.02452.xSearch in Google Scholar PubMed

Ekholm, E., Brattsand, M., and Egelrud, T. (2000). Stratum corneum tryptic enzyme in normal epidermis: a missing link in the desquamation process? J. Invest. Dermatol.114, 56–63.10.1046/j.1523-1747.2000.00820.xSearch in Google Scholar

Felber, L.M., Borgono, C.A., Cloutier, S.M., Kundig, C., Kishi, T., Ribeiro Chagas, J., Jichlinski, P., Gygi, C.M., Leisinger, H.J., Diamandis, E.P., and Deperthes, D. (2005). Enzymatic profiling of human kallikrein 14 using phage-display substrate technology. Biol. Chem.386, 291–298.10.1515/BC.2005.035Search in Google Scholar

Hägermark, O. (1974). Studies on experimental itch induced by kallikrein and bradykinin. Acta Derm. Venereol.54, 397–400.Search in Google Scholar

Hägermark, O. and Rajka, G. (1972). Experimental itch in human skin elicited by rat mast cell chymase. Acta Derm. Venereol.52, 125–128.10.2340/0001555552125128Search in Google Scholar

Hansson, L., Strömqvist, M., Bäckman, A., Wallbrandt, P., Carlstein, A., and Egelrud, T. (1994). Cloning, expression, and characterization of stratum corneum chymotryptic enzyme: a skin-specific human serine proteinase. J. Biol. Chem.269, 19420–19426.10.1016/S0021-9258(17)32185-3Search in Google Scholar

Hibino, T., Takemura, T., and Sato, K. (1994). Human eccrine sweat contains tissue kallikrein and kininase II. J. Invest. Dermatol.102, 214–220.10.1111/1523-1747.ep12371765Search in Google Scholar

Hooper, J.D., Bui, L.T., Rae, F.K., Harvey, T.J., Myers, S.A., Ashworth, L.K., and Clements, J.A. (2001). Identification and characterization of KLK14, a novel kallikrein serine protease gene located on human chromosome 19q13.4 and ex-pressed in prostate and skeletal muscle. Genomics73, 117–122.Search in Google Scholar

Horie, N., Fukuyama, K., Ito, Y., and Epstein, W.L. (1984). Detection and characterization of epidermal proteinases by polyacrylamide gel electrophoresis. Comp. Biochem. Physiol. B.77, 349–353.10.1016/0305-0491(84)90342-0Search in Google Scholar

Horie, N., Yokozeki, H., and Sato, K. (1986). Proteolytic enzymes in human eccrine sweat: a screening study. Am. J. Physiol.250, R691–698.10.1152/ajpregu.1986.250.4.R691Search in Google Scholar

Horikoshi, T., Arany, I., Rajaraman, S., Chen, S.H., Brysk, H., Lei, G., Tyring, S.K., and Brysk, M.M. (1998). Isoforms of cathepsin D and human epidermal differentiation. Biochimie80, 605–612.10.1016/S0300-9084(98)80013-8Search in Google Scholar

Kishi, T., Soosaipillai, A., Grass, L., Little, S.P., Johnstone, E.M., and Diamandis, E.P. (2004). Development of an immunofluorometric assay and quantification of human kallikrein 7 in tissue extracts and biological fluids. Clin. Chem.50, 709–716.10.1373/clinchem.2003.029538Search in Google Scholar PubMed

Komatsu, N., Takata, M., Otsuki, N., Toyama, T., Ohka, R., Takehara, K., and Saijoh, K. (2003). Expression and localization of tissue kallikrein mRNAs in human epidermis and appendages. J. Invest. Dermatol.121, 542–549.10.1046/j.1523-1747.2003.12363.xSearch in Google Scholar PubMed

Komatsu, N., Saijoh, K., Sidiropoulos, M., Tsai, B., Levesque, M.A., Elliott, M.B., Takehara, K., and Diamandis, E.P. (2005a). Quantification of human tissue kallikreins in the stratum corneum: dependence on age and gender. J. Invest. Dermatol.125, 1182–1189.10.1111/j.0022-202X.2005.23933.xSearch in Google Scholar PubMed

Komatsu, N., Saijoh, K., Toyama, T., Ohka, R., Otsuki, N., Hussack, G., Takehara, K., and Diamandis, E.P. (2005b). Multiple tissue kallikrein mRNA and protein expression in normal skin and skin diseases. Br. J. Dermatol.153, 274–281.10.1111/j.1365-2133.2005.06754.xSearch in Google Scholar

Komatsu, N., Tsai, B., Sidiropoulus, M., Saijoh, K., Levesque, M.A., Takehara, K., and Diamandis, E.P. (2006). Quantification of eight tissue kallikreins in the stratum corneum and sweat. J. Invest. Dermatol.126, 925–929.10.1038/sj.jid.5700146Search in Google Scholar

Laemmli, U.K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227, 680–685.10.1038/227680a0Search in Google Scholar

Lundström, A. and Egelrud, T. (1991). Stratum corneum chymotryptic enzyme: a proteinase which may be generally present in the stratum corneum and with a possible involvement in desquamation. Acta Derm. Venereol.71, 471–474.Search in Google Scholar

Lundwall, A., Band, V., Blaber, M., Clements, J., Courty, Y., Diamandis, E., Fritz, H., Lilja, H., Malm, J., Maltais, L.J., et al. (2006). A comprehensive nomenclature for serine proteases with homology to tissue kallikreins. Biol. Chem.387, 637–641.10.1515/BC.2006.082Search in Google Scholar

Matsudaira, P. (1987). Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes. J. Biol. Chem.262, 10035–10038.10.1016/S0021-9258(18)61070-1Search in Google Scholar

Poblete, M.T., Reynolds, N.J., Figueroa, C.D., Burton, J.L., Müller-Esterl, W., and Bhoola, K.D. (1991). Tissue kallikrein and kininogen in human sweat glands and psoriatic skin. Br. J. Dermatol.124, 236–241.10.1111/j.1365-2133.1991.tb00567.xSearch in Google Scholar PubMed

Rajka, G. (1967). Itch duration in the involved skin of atopic dermatitis (prurigo Besnier). Acta Derm. Venereol.47, 154–157.Search in Google Scholar

Sondell, B., Thornell, L.E., Stigbrand, T., and Egelrud, T. (1994). Immunolocalization of stratum corneum chymotryptic enzyme in human skin and oral epithelium with monoclonal antibodies: evidence of a proteinase specifically expressed in keratinizing squamous epithelia. J. Histochem. Cytochem.42, 459–465.10.1177/42.4.7510318Search in Google Scholar PubMed

Sondell, B., Dyberg, P., Anneroth, G.K., Ostman, P.O., and Egelrud, T. (1996). Association between expression of stratum corneum chymotryptic enzyme and pathological keratinization in human oral mucosa. Acta Derm. Venereol.76, 177–181.Search in Google Scholar

Sprecher, E., Chavanas, S., DiGiovanna, J.J., Amin, S., Nielsen, K., Prendiville, J.S., Silverman, R., Esterly, N.B., Spraker, M.K., Guelig, E., et al. (2001). The spectrum of pathogenic mutations in SPINK5 in 19 families with Netherton syndrome: implications for mutation detection and first case of prenatal diagnosis. J. Invest. Dermatol.117, 179–187.10.1046/j.1523-1747.2001.01389.xSearch in Google Scholar PubMed

Ständer, S. and Steinhoff, M. (2002). Pathophysiology of pruritus in atopic dermatitis: an overview. Exp. Dermatol.11, 12–24.10.1034/j.1600-0625.2002.110102.xSearch in Google Scholar PubMed

Suzuki, Y., Nomura, J., Hori, J., Koyama, J., Takahashi, M., and Horii, I. (1993). Detection and characterization of endogenous protease associated with desquamation of stratum corneum. Arch. Dermatol. Res.285, 372–377.10.1007/BF00371839Search in Google Scholar PubMed

Suzuki, Y., Koyama, J., Moro, O., Horii, I., Kikuchi, K., Tanida, M., and Tagami, H. (1996). The role of two endogenous proteases of the stratum corneum in degradation of desmoglein 1 and their reduced activity in the skin of ichtyotic patients. Br. J. Dermatol.134, 460–464.10.1046/j.1365-2133.1996.31794.xSearch in Google Scholar

Towbin, H.T., Staehelin, T., and Gordon, J. (1979). Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc. Natl. Acad. Sci. USA76, 4350–4354.10.1073/pnas.76.9.4350Search in Google Scholar PubMed PubMed Central

Travis, J. and Salvesen, G.S. (1983). Human plasma proteinase inhibitors. Annu. Rev. Biochem.52, 655–709.10.1146/annurev.bi.52.070183.003255Search in Google Scholar PubMed

Watkinson, A. (1999). Stratum corneum thiol protease (SCTP): a novel cysteine protease of late epidermal differentiation. Arch. Dermatol. Res.291, 260–268.10.1007/s004030050406Search in Google Scholar PubMed

Yousef, G.M. and Diamandis, E.P. (2001). The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr. Rev.22, 184–204.Search in Google Scholar

Yousef, G.M. and Diamandis, E.P. (2002). Human tissue kallikreins: a new enzymatic cascade pathway? Biol. Chem.383, 1045–1057.10.1515/BC.2002.113Search in Google Scholar PubMed

Yousef, G.M., Magklara, A., Chang, A., Jung, K., Katsaros, D., and Diamandis, E.P. (2001). Cloning of a new member of the human kallikrein gene family, KLK14, which is down-regulated in different malignancies. Cancer Res.61, 3425–3431.Search in Google Scholar

Yousef, G.M., Fracchioli, S., Scorilas, A. Borgono, C.A., Iskander, L., Puopolo, M., Massobrio, M., Diamandis, E.P., and Katsaros, D. (2003). Steroid hormone regulation and prognostic value of the human kallikrein gene 14 in ovarian cancer. Am. J. Clin. Pathol.119, 346–355.10.1309/0UA57MNAYV0MCE9USearch in Google Scholar PubMed

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

©2006 by Walter de Gruyter Berlin New York

Articles in the same Issue

  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)
Downloaded on 10.11.2025 from https://www.degruyterbrill.com/document/doi/10.1515/BC.2006.095/html?lang=en
Scroll to top button