Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer, skin disorders and other disease biomarkers.[8] This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Apart from its common transcript, an additional transcript variant has been described but its difference in function and full length nature has not been determined.[7]
KLK14 displays optimal trypsin-like activity at an alkaline pH of 8.0 and remains active in the pH ranges of 5.0 - 9.0 and is produced as a zymogen, but can function also in a chymotrypsin-like fashion.[9] Activation of KLK14 is mediated by KLK5 and after KLK14 activation, it further amplifies the activity of KLK proteases by a positive feedback loop via cleavage of pro-KLK5, which is a central player in KLK cascade.[10][11] KLK14 function has not yet been fully elucidated, but its most notable substrate is PAR2.[12][13] Its activity is inhibited by a wide variety of proteins, like macroglobulins, serpins, and the serine protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI) and also micro-environmental pH; and single-metal-ion inhibitors of KLKs among others.[14]
^"Proceedings of the 1st International Symposium on Kallikreins, Lausanne, Switzerland, September 1-3 , 2005". Biological Chemistry. 387 (6): 635–824. June 2006. doi:10.1515/BC.2006.081. PMID16800723.
^Prassas I, Eissa A, Poda G, Diamandis EP (March 2015). "Unleashing the therapeutic potential of human kallikrein-related serine proteases". Nature Reviews. Drug Discovery. 14 (3): 183–202. doi:10.1038/nrd4534. PMID25698643.
^Brattsand M, Stefansson K, Lundh C, Haasum Y, Egelrud T (January 2005). "A proteolytic cascade of kallikreins in the stratum corneum". The Journal of Investigative Dermatology. 124 (1): 198–203. doi:10.1111/j.0022-202x.2004.23547.x. PMID15654974.
^Eissa A, Diamandis EP (June 2008). "Human tissue kallikreins as promiscuous modulators of homeostatic skin barrier functions". Biological Chemistry. 389 (6): 669–80. doi:10.1515/bc.2008.079. PMID18627299.
^Hachem JP, Man MQ, Crumrine D, Uchida Y, Brown BE, Rogiers V, et al. (September 2005). "Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity". The Journal of Investigative Dermatology. 125 (3): 510–20. doi:10.1111/j.0022-202x.2005.23838.x. PMID16117792.
^Hachem JP, Wagberg F, Schmuth M, Crumrine D, Lissens W, Jayakumar A, et al. (July 2006). "Serine protease activity and residual LEKTI expression determine phenotype in Netherton syndrome". The Journal of Investigative Dermatology. 126 (7): 1609–21. doi:10.1038/sj.jid.5700288. PMID16601670.
^Swedberg JE, Veer SJ, Harris JM (2012). "Natural, engineered and synthetic inhibitors of kallikrein-related peptidases.". In Magdolen V, Sommerhoff CP, Fritz H, Schmitt M (eds.). Kallikrein-Related Peptidases. Vol. 1: Characterization, regulation, and interactions within the proteas e. Walter de Gruyter GmbH. pp. 141–160. doi:10.1515/9783110260373.141. ISBN978-3-11-026037-3.
Yousef GM, Magklara A, Chang A, Jung K, Katsaros D, Diamandis EP (April 2001). "Cloning of a new member of the human kallikrein gene family, KLK14, which is down-regulated in different malignancies". Cancer Research. 61 (8): 3425–31. PMID11309303.
Hooper JD, Bui LT, Rae FK, Harvey TJ, Myers SA, Ashworth LK, Clements JA (April 2001). "Identification and characterization of KLK14, a novel kallikrein serine protease gene located on human chromosome 19q13.4 and expressed in prostate and skeletal muscle". Genomics. 73 (1): 117–22. doi:10.1006/geno.2000.6490. PMID11352573.
Yousef GM, Stephan C, Scorilas A, Ellatif MA, Jung K, Kristiansen G, et al. (September 2003). "Differential expression of the human kallikrein gene 14 (KLK14) in normal and cancerous prostatic tissues". The Prostate. 56 (4): 287–92. doi:10.1002/pros.10263. PMID12858357.
Brattsand M, Stefansson K, Lundh C, Haasum Y, Egelrud T (January 2005). "A proteolytic cascade of kallikreins in the stratum corneum". The Journal of Investigative Dermatology. 124 (1): 198–203. doi:10.1111/j.0022-202X.2004.23547.x. PMID15654974.
Felber LM, Borgoño CA, Cloutier SM, Kündig C, Kishi T, Ribeiro Chagas J, et al. (March 2005). "Enzymatic profiling of human kallikrein 14 using phage-display substrate technology". Biological Chemistry. 386 (3): 291–8. doi:10.1515/BC.2005.035. PMID15843175.
Stefansson K, Brattsand M, Ny A, Glas B, Egelrud T (June 2006). "Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum". Biological Chemistry. 387 (6): 761–8. doi:10.1515/BC.2006.095. PMID16800737.