Activation profiles of human kallikrein-related peptidases by matrix metalloproteinases

Michael Blaber, Hyesook Yoon, Sachiko I. Blaber, Wu Li, Isobel A Scarisbrick

Research output: Contribution to journalArticle

24 Citations (Scopus)

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 propeptide, 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.

Original languageEnglish (US)
Pages (from-to)137-147
Number of pages11
JournalBiological Chemistry
Volume394
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Kallikreins
Matrix Metalloproteinase 20
Matrix Metalloproteinases
Peptide Hydrolases
Chemical activation
Neurodegenerative diseases
Biomarkers
Liquefaction
Semen
Neurodegenerative Diseases
Skin
Research Personnel
Inflammation
Neoplasms
Therapeutics

Keywords

  • Activation cascade
  • Enamelysin
  • Kallikreinrelated peptidase (KLK)
  • Matrix metalloproteinase 20 (MMP-20)

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology

Cite this

Activation profiles of human kallikrein-related peptidases by matrix metalloproteinases. / Blaber, Michael; Yoon, Hyesook; Blaber, Sachiko I.; Li, Wu; Scarisbrick, Isobel A.

In: Biological Chemistry, Vol. 394, No. 1, 01.2013, p. 137-147.

Research output: Contribution to journalArticle

Blaber, Michael ; Yoon, Hyesook ; Blaber, Sachiko I. ; Li, Wu ; Scarisbrick, Isobel A. / Activation profiles of human kallikrein-related peptidases by matrix metalloproteinases. In: Biological Chemistry. 2013 ; Vol. 394, No. 1. pp. 137-147.
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