title: A proteolytic cascade of kallikreins in the stratum corneum.
abstract: Serine proteases belonging to the kallikrein group may play a central role in desquamation. We have identified human kallikreins 5, 7, and 14 (hK5, hK7, hK14) in catalytically active form in stratum corneum. All three enzymes are produced as inactive precursors. In this work, we prepared recombinant enzymes and enzyme precursors and characterized the catalytic properties of hK5 and hK14. With peptide substrates hK5 and hK14 both showed trypsin-like specificity and alkaline pH-optima. For the substrates tested, hK14 was superior to hK5 as regards maximum catalytic rate as well as catalytic efficiency. hK5, but not hK14, could activate pro-hK7 in a reaction which was optimal at pH 5-7. hK5 could activate its own precursor as well as pro-hK14. This was in contrast to hK14, which could activate pro-hK5 but not its own precursor. The activation of pro-hK5 either by auto-activation or by hK14 occurred at maximum rate at neutral or weakly alkaline pH, whereas activation of pro-hK14 by hK5 was optimal at pH 6-7. We conclude that the enzymes studied may be part of a protease cascade in the stratum corneum, and that the observed pH effects may have physiological relevance.
authors.affiliation: Department of Public Health and Clinical Medicine, Dermatology and Venereology, Umeå University, Umeå, Sweden. maria.brattsand@dermven.umu.se
authors.forename: Maria
authors.initials: M
authors.lastname: Brattsand
authors.forename: Kristina
authors.initials: K
authors.lastname: Stefansson
authors.forename: Christine
authors.initials: C
authors.lastname: Lundh
authors.forename: Ylva
authors.initials: Y
authors.lastname: Haasum
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Egelrud
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007313:Insecta; D007610:Kallikreins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D010455:Peptides; C425336:KLK14 protein, human; C400147:KLK5 protein, human; C082472:KLK7 protein, human; D007610:Kallikreins; D012697:Serine Endopeptidases