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Kallikrein-related peptidases: bridges between immune functions and extracellular matrix degradation

  • Georgia Sotiropoulou and Georgios Pampalakis
Published/Copyright: February 24, 2010
Biological Chemistry
From the journal Volume 391 Issue 4

Abstract

Kallikrein-related peptidases (KLKs) constitute a family of 15 highly conserved serine proteases encoded by the largest uninterrupted cluster of protease-encoding genes within the human genome. Recent studies, mostly relying on in vitro proteolysis of recombinant proteins, have suggested that KLK activities are regulated by proteolytic activation cascades that can operate in a tissue-specific manner, such as the semen liquefaction and skin desquamation cascades. The validity of KLK activation cascades in vivo largely remains to be demonstrated. Here, we focus on recent investigations showing that KLKs represent interesting players in the broader field of immunology based on their ability to bridge their inherent ability to degrade the extracellular matrix with major functions of the immune system. More specifically, KLKs assist in the infiltration of immune cells through the skin and the blood brain barrier, whereas they catalyze the generation of antimicrobial peptides by proteolytic activation and further processing of protein precursors. In an attempt to integrate current knowledge, we propose KLK-mediated pathways that are putatively involved in inflammation associated with skin wounding and central nervous system disorders, including multiple sclerosis. Finally, we present evidence of KLK participation in autoimmune diseases and allergies.


Corresponding authors ;

Received: 2009-10-10
Accepted: 2009-12-18
Published Online: 2010-02-24
Published in Print: 2010-04-01

©2010 by Walter de Gruyter Berlin New York

Articles in the same Issue

  1. Guest Editorial
  2. The 3rd International Symposium on Kallikreins and Kallikrein-Related Peptidases
  3. HIGHLIGHT: 3RD INTERNATIONAL SYMPOSIUM ON KALLIKREINS AND KALLIKREIN-RELATED PEPTIDASES
  4. Kallikrein-related peptidases: proteolysis and signaling in cancer, the new frontier
  5. Functional intersection of the kallikrein-related peptidases (KLKs) and thrombostasis axis
  6. Kallikrein-related peptidases: bridges between immune functions and extracellular matrix degradation
  7. Prostate-specific antigen: an overlooked candidate for the targeted treatment and selective imaging of prostate cancer
  8. Tissue kallikrein in cardiovascular, cerebrovascular and renal diseases and skin wound healing
  9. Natural and engineered kallikrein inhibitors: an emerging pharmacopoeia
  10. Klk8, a multifunctional protease in the brain and skin: analysis of knockout mice
  11. Functional proteomics of kallikrein-related peptidases in ovarian cancer ascites fluid
  12. Polyclonal antibodies against kallikrein-related peptidase 4 (KLK4): immunohistochemical assessment of KLK4 expression in healthy tissues and prostate cancer
  13. Immunohistochemical analysis of kallikrein-related peptidases in the normal kidney and renal tumors: potential clinical implications
  14. Dysregulation of kallikrein-related peptidases in renal cell carcinoma: potential targets of miRNAs
  15. Analysis of an engineered plasma kallikrein inhibitor and its effect on contact activation
  16. Increased blood pressure and water intake in transgenic mice expressing rat tonin in the brain
  17. A structural network associated with the kallikrein-kinin and renin-angiotensin systems
  18. Analyzing the protease web in skin: meprin metalloproteases are activated specifically by KLK4, 5 and 8 vice versa leading to processing of proKLK7 thereby triggering its activation
  19. Expression of PSA-RP2, an alternatively spliced variant from the PSA gene, is increased in prostate cancer tissues but the protein is not secreted from prostate cancer cells
  20. KLK5 gene expression is severely upregulated in androgen-independent prostate cancer cells after treatment with the chemotherapeutic agents docetaxel and mitoxantrone
  21. Identification of IGFBP-3 fragments generated by KLK2 and prevention of fragmentation by KLK2-inhibiting peptides
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