title: Activation profiles of human kallikrein-related peptidases by matrix metalloproteinases.
abstract: The 15 human kallikrein-related peptidases (KLKs) are clinically important biomarkers and therapeutic targets of interest in inflammation, cancer, and neurodegenerative disease. KLKs are secreted as inactive pro-forms (pro-KLKs) that are activated extracellularly by specific proteolytic release of their amino-terminal pro-peptide, and this is a key step in their functional regulation. Physiologically relevant KLK regulatory cascades of activation have been described in skin desquamation and semen liquefaction, and work by a large number of investigators has elucidated pairwise and autolytic activation relationships among the KLKs with the potential for more extensive activation cascades. More recent work has asked whether functional intersection of KLKs with other types of regulatory proteases exists. Such studies show a capacity for members of the thrombostasis axis to act as broad activators of pro-KLKs. In the present report, we ask whether such functional intersection is possible between the KLKs and the members of the matrix metalloproteinase (MMP) family by evaluating the ability of the MMPs to activate pro-KLKs. The results identify MMP-20 as a broad activator of pro-KLKs, suggesting the potential for intersection of the KLK and MMP axes under pathological dysregulation of MMP-20 expression.
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306-4300, USA.
authors.forename: Hyesook
authors.initials: H
authors.lastname: Yoon
authors.forename: Sachiko I
authors.initials: SI
authors.lastname: Blaber
authors.forename: Wu
authors.initials: W
authors.lastname: Li
authors.forename: Isobel A
authors.initials: IA
authors.lastname: Scarisbrick
authors.forename: Michael
authors.initials: M
authors.lastname: Blaber
mesh_terms: D004789:Enzyme Activation; D006801:Humans; D006868:Hydrolysis; D007610:Kallikreins / Q000378:metabolism*; D053519:Matrix Metalloproteinase 20 / Q000378:metabolism*
chemical_list: D007610:Kallikreins; D053519:Matrix Metalloproteinase 20