Kallikrein-related peptidase 7 (KLK7) is a serine protease that in humans is encoded by the KLK7gene.[1][2][3][4] KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme (SCCE).[5] It was later identified as the seventh member of the human kallikrein family, which includes fifteen homologous serine proteases located on chromosome 19 (19q13).[6]
Alternative splicing of the KLK7 gene results in two transcript variants encoding the same protein.[4]
Function
KLK7 is secreted as an inactive zymogen in the stratum granulosum layer of the epidermis, requiring proteolytic cleavage of the short N-terminal pro-region to liberate activated enzyme. This may be performed by KLK5 or matriptase, which are in vitro activators of KLK7.[7][8]
Once active, KLK7 is able to cleave desmocollin and corneodesmosin.[9] These proteins constitute the extracellular component of corneodesmosomes, intercellular cohesive structures which link the intermediate filaments of adjacent cells in the stratum corneum. Proteolysis of corneodesmosomes is required for desquamation, the shedding of corneocytes from the outer layer of the epidermis. This indicates a role for KLK7 in maintaining skin homeostasis.
Both KLK5 and KLK14, other skin-expressed proteases, also cleave corneodesmosomal proteins.[9] KLK5 is able to undergo autoactivation, as well as activating KLK7 and KLK14, suggesting a KLK skin cascade is responsible for coordinating desquamation.[8]
KLK7 is a chymotrypsin-like serine protease, preferring to cleave proteins at the residues tyrosine, phenylalanine or leucine.[15] Analysis of peptide substrate hydrolysis indicates a strong preference for tyrosine at P1.[16]
Clinical significance
Skin disease
Dysregulation of KLK7 has been linked to several skin disorders including atopic dermatitis,[17][18]psoriasis[19] and Netherton syndrome.[20][21] These diseases are characterised by excessively dry, scaly and inflamed skin, due to a disruption of skin homeostasis and correct barrier function.
↑Hansson L, Stromqvist M, Backman A, Wallbrandt P, Carlstein A, Egelrud T (Aug 1994). "Cloning, expression, and characterization of stratum corneum chymotryptic enzyme. A skin-specific human serine proteinase". J Biol Chem. 269 (30): 19420–6. PMID8034709.
↑Lundwall A, Band V, Blaber M, Clements JA, Courty Y, Diamandis EP, Fritz H, Lilja H, Malm J, Maltais LJ, Olsson AY, Petraki C, Scorilas A, Sotiropoulou G, Stenman UH, Stephan C, Talieri M, Yousef GM (Jun 2006). "A comprehensive nomenclature for serine proteases with homology to tissue kallikreins". Biol Chem. 387 (6): 637–41. doi:10.1515/BC.2006.082. PMID16800724.
↑Diamandis, Eleftherios P.; Deperthes, David; Lundwall, Åke (Jun 2006). "Proceedings of the 1st International Symposium on Kallikreins, Lausanne, Switzerland, September 1-3 , 2005". Biol Chem. 387 (6): 635–824. doi:10.1515/BC.2006.081. PMID16800723.
↑Lundstrom A, 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 Dermato-Venereologica. 71 (6): 471–474. PMID1685827.
↑Yousef GM, Scorilas A, Magklara A, et al. (2000). "The KLK7 (PRSS6) gene, encoding for the stratum corneum chymotryptic enzyme is a new member of the human kallikrein gene family - genomic characterization, mapping, tissue expression and hormonal regulation". Gene. 254 (1–2): 119–28. doi:10.1016/S0378-1119(00)00280-8. PMID10974542.
↑ 8.08.1Brattsand, M., Stefansson, K., Lundh, C., Haasum, Y., & Egelrud, T. (2005). "A proteolytic cascade of kallikreins in the stratum corneum". Journal of Investigative Dermatology. 124 (1): 198–203. doi:10.1111/j.0022-202X.2004.23547.x. PMID15654974.CS1 maint: Multiple names: authors list (link)
↑ 9.09.1Caubet C, Jonca N, Brattsand M, et al. (2004). "Degradation of corneodesmosome proteins by two serine proteases of the kallikrein family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7". J. Invest. Dermatol. 122 (5): 1235–44. doi:10.1111/j.0022-202X.2004.22512.x. PMID15140227.
↑Egelrud T, Brattsand M, Kreutzmann P, Walden M, Vitzithum K, Marx UC, Forssmann WG, Mägert HJ (2005). "hK5 and hK7, two serine proteinases abundant in human skin, are inhibited by LEKTI domain 6". Br J Dermatol. 153 (6): 1200–1203. doi:10.1111/j.1365-2133.2005.06834.x.
↑ 13.013.1Franzke CW, Baici A, Bartels J, Christophers E, Wiedow O (September 1996). "Antileukoprotease inhibits stratum corneum chymotryptic enzyme. Evidence for a regulative function in desquamation". J Biol Chem. 271 (36): 21886–90. doi:10.1074/jbc.271.36.21886.
↑Galliano MF, Toulza E, Gallinaro H, Jonca N, Ishida-Yamamoto A, Serre G, Guerrin M (November 2005). "A novel protease inhibitor of the alpha2-macroglobulin family expressed in the human epidermis". J Biol Chem. 281 (9): 5780–5789. doi:10.1074/jbc.m508017200. PMID16298998.
↑Skytt A, Strömqvist M, Egelrud T (1995). "Primary substrate specificity of recombinant human stratum corneum chymotryptic enzyme". Biochem. Biophys. Res. Commun. 211 (2): 586–9. doi:10.1006/bbrc.1995.1853. PMID7794273.
↑Debela M, Magdolen V, Schechter N, Valachova M, Lottspeich F, Craik CS, Choe Y, Bode W, Goettig P (2006). "Specificity profiling of seven human tissue kallikreins reveals individual subsite preferences". J Biol Chem. 281 (35): 25678–88. doi:10.1074/jbc.M602372200. PMID16740631.
↑Komatsu N, Saijoh K, Kuk C, Liu AC, Khan S, Shirasaki F, Takehara K, Diamandis EP (Jun 2007). "Human tissue kallikrein expression in the stratum corneum and serum of atopic dermatitis patients". Exp Dermatol. 16 (6): 513–519. doi:10.1111/j.1600-0625.2007.00562.x. PMID17518992.
↑Vasilopoulos Y, Cork MJ, Murphy R, et al. (2004). "Genetic association between an AACC insertion in the 3'UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis". J. Invest. Dermatol. 123 (1): 62–6. doi:10.1111/j.0022-202X.2004.22708.x. PMID15191543.
↑Ekholm E, Egelrud T (Apr 1999). "Stratum corneum chymotryptic enzyme in psoriasis". Arch Dermatol Res. 291 (4): 195–200. doi:10.1007/s004030050393. PMID10335915.
↑Descargues P, Deraison C, Bonnart C, Kreft M, Kishibe M, Ishida-Yamamoto A, Elias P, Barrandon Y, Zambruno G, Sonnenberg A, Hovnanian A (Jan 2005). "Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity". Nat Genet. 37 (1): 56–65. doi:10.1038/ng1493. PMID15619623.
↑Descargues P, Deraison C, Prost C, et al. (2006). "Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin- and chymotrypsin-like hyperactivity in Netherton syndrome". J. Invest. Dermatol. 126 (7): 1622–32. doi:10.1038/sj.jid.5700284. PMID16628198.
↑Dong Y, Kaushal A, Brattsand M, et al. (2004). "Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers". Clin. Cancer Res. 9 (5): 1710–20. PMID12738725.
↑Talieri M, Diamandis EP, Gourgiotis D, Mathioudaki K, Scorilas A (2004). "Expression analysis of the human kallikrein 7 (KLK7) in breast tumors: a new potential biomarker for prognosis of breast carcinoma". Thromb Haemost. 91 (1): 180–186. doi:10.1267/THRO04010180. PMID14691584.
↑Santin AD, Cane' S, Bellone S, et al. (2004). "The serine protease stratum corneum chymotryptic enzyme (kallikrein 7) is highly overexpressed in squamous cervical cancer cells". Gynecol. Oncol. 94 (2): 283–8. doi:10.1016/j.ygyno.2004.05.023. PMID15297163.
↑Rezze GG; Fregnani JHTG; Duprat J; Landman G (2011). "Cell adhesion and communication proteins are differentially expressed in melanoma progression model". Hum Pathol. 42 (3): 409–418. doi:10.1016/j.humpath.2010.09.004. PMID21193224.
↑Planque C, de Monte M, Guyetant S, et al. (2005). "KLK5 and KLK7, two members of the human tissue kallikrein family, are differentially expressed in lung cancer". Biochem. Biophys. Res. Commun. 329 (4): 1260–6. doi:10.1016/j.bbrc.2005.02.100. PMID15766562.
Further reading
Gan L, Lee I, Smith R, et al. (2001). "Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region". Gene. 257 (1): 119–30. doi:10.1016/S0378-1119(00)00382-6. PMID11054574.
Diamandis EP, Scorilas A, Kishi T, et al. (2004). "Altered kallikrein 7 and 10 concentrations in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia". Clin. Biochem. 37 (3): 230–7. doi:10.1016/j.clinbiochem.2003.11.012. PMID14972646.
Ishida-Yamamoto A, Deraison C, Bonnart C, et al. (2005). "LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum". J. Invest. Dermatol. 124 (2): 360–6. doi:10.1111/j.0022-202X.2004.23583.x. PMID15675955.
Yamasaki K, Schauber J, Coda A, et al. (2006). "Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin". FASEB J. 20 (12): 2068–80. doi:10.1096/fj.06-6075com. PMID17012259.