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Human kallikrein 4: enzymatic activity, inhibition, and degradation of extracellular matrix proteins

  • Chistina V. Obiezu , Iacovos P. Michael , Michael A. Levesque and Eleftherios P. Diamandis
Published/Copyright: June 26, 2006
Biological Chemistry
From the journal Volume 387 Issue 6

Abstract

Human kallikrein 4 (hK4) is a member of the expanded family of human kallikreins, a group of 15 secreted proteases. While this protein has been associated with ovarian and prostate cancer prognosis, only limited functional information exists. Therefore, we have undertaken an investigation of its enzymatic properties regarding substrate preference, degradation of extracellular matrix proteins, and its inhibition by various inhibitors. We successfully expressed and purified active recombinant hK4 from supernatants of the Pichia pastoris expression system. This enzyme seems to cleave more efficiently after Arg compared to Lys at the P1 position and exhibits modest specificity for amino acids at positions P2 and P3. hK4 forms complexes with α1-antitrypsin, α2-antiplasmin and α2-macroglobulin. The protease mediates limited degradation of extracellular matrix proteins such as collagen I and IV, and more efficient degradation of the α-chain of fibrinogen. The cleavage of extracellular matrix proteins by hK4 suggests that this enzyme may play a role in tissue remodeling and cancer metastasis.

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Published Online: 2006-06-26
Published in Print: 2006-06-01

©2006 by Walter de Gruyter Berlin New York

Articles in the same Issue

  1. The First International Symposium on Kallikreins
  2. A comprehensive nomenclature for serine proteases with homology to tissue kallikreins
  3. The kallikrein world: an update on the human tissue kallikreins
  4. Cellular distribution of human tissue kallikreins: immunohistochemical localization
  5. The tissue kallikrein-kinin system protects against cardiovascular and renal diseases and ischemic stroke independently of blood pressure reduction
  6. Proteinase-mediated cell signalling: targeting proteinase-activated receptors (PARs) by kallikreins and more
  7. Recombinant kallikrein expression: site-specific integration for hK6 production in human cells
  8. Kallikrein-related peptidase (KLK) family mRNA variants and protein isoforms in hormone-related cancers: do they have a function?
  9. The role of kallikrein-related peptidases in prostate cancer: potential involvement in an epithelial to mesenchymal transition
  10. Human kallikrein 10, a predictive marker for breast cancer
  11. Activation and enzymatic characterization of recombinant human kallikrein 8
  12. Human tissue kallikrein 9: production of recombinant proteins and specific antibodies
  13. The human kallikrein 10 promoter contains a functional retinoid response element
  14. Human kallikrein 4: enzymatic activity, inhibition, and degradation of extracellular matrix proteins
  15. Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum
  16. A sensitive proximity ligation assay for active PSA
  17. Multiple mechanisms underlie the aberrant expression of the human kallikrein 6 gene in breast cancer
  18. Expression of the human kallikrein genes 10 (KLK10) and 11 (KLK11) in cancerous and non-cancerous lung tissues
  19. mRNA expression analysis of human kallikrein 11 (KLK11) may be useful in the discrimination of benign prostatic hyperplasia from prostate cancer after needle prostate biopsy
  20. The epigenetic basis for the aberrant expression of kallikreins in human cancers
  21. Improved prostate cancer detection with a human kallikrein 11 and percentage free PSA-based artificial neural network
  22. Overexpression of the human tissue kallikrein genes KLK4, 5, 6, and 7 increases the malignant phenotype of ovarian cancer cells
  23. Inhibition profiles of human tissue kallikreins by serine protease inhibitors
  24. Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs)
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