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Putative kallikrein substrates and their (patho)biological functions

  • Yijing Yu

    Yijing Yu completed her Msc Degree in the Molecular Science program at Ryerson University, Ontario, Canada. Currently, she is a PhD candidate at the Department of Laboratory Medicine and Pathobiology at the University of Toronto, Ontario, Canada. Her main research interests include the identification of novel biological substrates of kallikreins using degradomic approaches and the development of new therapeutic targets for skin diseases.

    , Ioannis Prassas

    Ioannis Prassas obtained his PhD from the Department of Laboratory Medicine and Pathobiology at the University of Toronto, Ontario, Canada. Currently, he is training as a post-doctoral fellow in the Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Onrario, Canada. His main research activities evolve around the use of mass spectrometry for the identification of novel therapeutic targets and the development of new therapeutic agents.

    and Eleftherios P. Diamandis

    Eleftherios Diamandis currently serves as the Division Head of Clinical Biochemistry at Mount Sinai Hospital and Biochemist-in-Chief at the University Health Network and is Professor & Head, Clinical Biochemisty, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada. His research activities evolve around discovery and validation of cancer biomarkers, proteomics, mass spectrometry and translational research.

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Published/Copyright: April 11, 2014

Abstract

Human tissue kallikreins (KLKs) represent the largest contiguous group of protease genes within our genome. All 15 KLK genes co-localize within approximately 260 kb in human chromosome 19q13.3–13.4 (14 640 kb→274 990 kb). They are widely expressed in several tissues and mediate a wide range of critical physiological and pathological processes. Despite the recent developments in KLK research, elucidation of their physiological substrate repertoires remains a largely unfulfilled goal. Phage display, positional scanning and combinatorial peptide library screens have provided some valuable insights into the preferred specificities of these powerful enzymes. More recently, advances in proteomic technologies have enabled more systemic approaches towards identification of KLK substrates in a physiological setting. The advent of degradomic technologies has brought to light several putative physiological substrates and has allowed a deeper appreciation of the in vivo functional roles of KLKs. The aim of this review is to provide an overview of the different techniques that have been utilized towards the elucidation of the substrate specificities of these enzymes and elaborate on their emerging in vivo substrates.


Corresponding author: Eleftherios P. Diamandis, MD, PhD, Pathology and Laboratory Medicine Department, Mount Sinai Hospital Suite 6-201, Box 32, 60 Murray Street Toronto, ON, M5T 3L9, Canada, Phone: +14165868443, Fax: +14166195521, e-mail:

About the authors

Yijing Yu

Yijing Yu completed her Msc Degree in the Molecular Science program at Ryerson University, Ontario, Canada. Currently, she is a PhD candidate at the Department of Laboratory Medicine and Pathobiology at the University of Toronto, Ontario, Canada. Her main research interests include the identification of novel biological substrates of kallikreins using degradomic approaches and the development of new therapeutic targets for skin diseases.

Ioannis Prassas

Ioannis Prassas obtained his PhD from the Department of Laboratory Medicine and Pathobiology at the University of Toronto, Ontario, Canada. Currently, he is training as a post-doctoral fellow in the Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Onrario, Canada. His main research activities evolve around the use of mass spectrometry for the identification of novel therapeutic targets and the development of new therapeutic agents.

Eleftherios P. Diamandis

Eleftherios Diamandis currently serves as the Division Head of Clinical Biochemistry at Mount Sinai Hospital and Biochemist-in-Chief at the University Health Network and is Professor & Head, Clinical Biochemisty, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada. His research activities evolve around discovery and validation of cancer biomarkers, proteomics, mass spectrometry and translational research.

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Received: 2014-2-13
Accepted: 2014-4-8
Published Online: 2014-4-11
Published in Print: 2014-9-1

©2014 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: The 5th International Symposium on Kallikreins and Kallikrein-Related Peptidases
  4. KLKs and their hormone-like signaling actions: a new life for the PSA-KLK family
  5. Putative kallikrein substrates and their (patho)biological functions
  6. Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy
  7. Sweetened kallikrein-related peptidases (KLKs): glycan trees as potential regulators of activation and activity
  8. Activation of membrane-bound proteins and receptor systems: a link between tissue kallikrein and the KLK-related peptidases
  9. Kallikreins are involved in an miRNA network that contributes to prostate cancer progression
  10. Evolution of Klk4 and enamel maturation in eutherians
  11. Growth and survival of lung cancer cells: regulation by kallikrein-related peptidase 6 via activation of proteinase-activated receptor 2 and the epidermal growth factor receptor
  12. CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation
  13. Mining for single nucleotide variants (SNVs) at the kallikrein locus with predicted functional consequences
  14. Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short-term relapse in patients with laryngeal squamous cell carcinoma
  15. Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response
  16. Kallikrein-related peptidase 7 (KLK7) is a proliferative factor that is aberrantly expressed in human colon cancer
  17. Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer
  18. Loss of miR-378 in prostate cancer, a common regulator of KLK2 and KLK4, correlates with aggressive disease phenotype and predicts the short-term relapse of the patients
  19. Kallikrein-related peptidase 6 (KLK6) expression in the progression of colon adenoma to carcinoma
  20. Development of monoclonal antibodies to human kallikrein-related peptidase 6 (KLK6) and their use in an immunofluorometric assay for free KLK6
  21. Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer
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