Major role of human KLK14 in seminal clot liquefaction

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Bibtex

@article{8e059f7bd00b4cd8b098a0e8570ac5b3,
title = "Major role of human KLK14 in seminal clot liquefaction",
abstract = "Liquefaction of human semen involves proteolytic degradation of the seminal coagulum and release of motile spermatozoa. Several members of human kallikrein-related peptidases (KLKs) have been implicated in semen liquefaction, functioning through highly regulated proteolytic cascades. Among these, KLK3 (also known as prostate-specific antigen) is the main executor enzyme responsible for processing of the primary components of semen coagulum, semenogelins I and II. We have recently identified KLK14 as a potential activator of KLK3 and other KLKs. This study aims to elucidate the cascade-mediated role of KLK14 ex vivo. KLK14 expression was significantly lower (p = 0.0252) in individuals with clinically delayed liquefaction. Concordantly, KLK14 expression was significantly (p = 0.0478) lower in asthenospermic cases. Specific inhibition of KLK14 activity by the synthetic inhibitor ACT(G9) resulted in a significant delay in semen liquefaction, a drop in the {"}early{"} (30 min postejaculation) {"}chymotrypsin- like{"} and KLK1 activity, and an increase in the {"}late{"} (90 min postejaculation) chymotrypsin-like activity. Conversely, the addition of recombinant active KLK14 facilitated the liquefaction process, augmented the early chymotrypsin-like activity, and lowered late chymotrypsin-like activity. Given that the observed chymotrypsin-like activity was almost completely attributed to KLK3 activity, KLK3 seems to be regulated bidirectionally. Accordingly, a higher level of KLK3 fragmentation was observed in KLK14-induced coagula, suggesting an inactivation mechanism via internal cleavage. Finally, semenogelins I and II were directly cleaved by KLK14. Semenogelins were also able to reverse KLK14 inhibition by Zn2+, providing a novel regulatory mechanism for KLK14 activity. Our results show that KLK14 exerts a significant and dose-dependent effect in the process of semen liquefaction.",
author = "Nashmil Emami and David Deperthes and Johan Malm and Diamandis, {Eleftherios P}",
year = "2008",
doi = "10.1074/jbc.M801194200",
language = "English",
volume = "283",
pages = "19561--19569",
journal = "Journal of Biological Chemistry",
issn = "1083-351X",
publisher = "ASBMB",
number = "28",

}