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KLKs and their hormone-like signaling actions: a new life for the PSA-KLK family

  • Since the late 1960s, Hollenberg has made sustained and conceptually paradigm-shifting contributions in the area of molecular pharmacology of hormone action as related to signaling by hormone-like mediators including insulin, epidermal growth factor, and proteolytic enzymes. He is also a professional artist, whose focus is on Chinese brushwork. His work can be found in international collections. His scientific contributions have been recognized by membership in the Royal Society of Canada and a number of research-related awards: (1) the Pharmacological Society of Canada’s 1999 Novartis award for outstanding contributions to pharmacology in Canada, (2) the Canadian Society of Clinical Investigation (CSCI) 2009 Distinguished Scientist award, (3) the Royal Society of Canada’s 2011 McLaughlin medal for sustained research excellence, (4) just recently, the CSCI/Royal College Henry Friesen Award for 2012 for demonstrated leadership in developing biomedical research at local, national, and international levels, and (5) the 2013 The E.K. Frey-E. Werle Commemorative Gold Medal for outstanding contributions on the role of the kallikrein-kinin system and related subjects in health and disease and with significant influence on the development in these fields.

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Published/Copyright: August 6, 2014
Biological Chemistry
From the journal Biological Chemistry Volume 395 Issue 9

Abstract

Human kallikrein-related peptidases (KLKs), including the well-known prostate cancer biomarker, prostate-specific antigen (PSA-KLK3), along with 14 other serine proteinase KLK family members are now known to regulate cells by cleaving and activating members of the G-protein-coupled proteinase-activated receptor (PAR) family. This hormone-like signaling action of the KLKs has provided a new perspective for understanding the biological roles that KLKs may play in normal and pathophysiological settings. This overview summarizes the circumstances leading up to the discovery of this action of the KLKs and provides an overview of the diverse impact on tissue function that may result from KLK-triggered PAR activation.

Keywords: inflammation; prostate-specific antigen (PSA); protease-activated receptors; proteinase-activated receptors (PARs); signal transduction
Corresponding author: Morley D. Hollenberg, Faculty of Medicine, Department of Physiology and Pharmacology and Department of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1, e-mail:

About the author

Morley D. Hollenberg

Since the late 1960s, Hollenberg has made sustained and conceptually paradigm-shifting contributions in the area of molecular pharmacology of hormone action as related to signaling by hormone-like mediators including insulin, epidermal growth factor, and proteolytic enzymes. He is also a professional artist, whose focus is on Chinese brushwork. His work can be found in international collections. His scientific contributions have been recognized by membership in the Royal Society of Canada and a number of research-related awards: (1) the Pharmacological Society of Canada’s 1999 Novartis award for outstanding contributions to pharmacology in Canada, (2) the Canadian Society of Clinical Investigation (CSCI) 2009 Distinguished Scientist award, (3) the Royal Society of Canada’s 2011 McLaughlin medal for sustained research excellence, (4) just recently, the CSCI/Royal College Henry Friesen Award for 2012 for demonstrated leadership in developing biomedical research at local, national, and international levels, and (5) the 2013 The E.K. Frey-E. Werle Commemorative Gold Medal for outstanding contributions on the role of the kallikrein-kinin system and related subjects in health and disease and with significant influence on the development in these fields.

Acknowledgments

Publications and unpublished data forming the basis of this overview were supported in large part by the Canadian Institutes of Health Research, The Heart and Stroke Foundation of Alberta, Nunavut and Northwest Territories, a Discovery Grant from Prostate Cancer Canada, and by scholarship support for postdoctoral trainees from the Alberta Heritage Foundation for Medical Research (now termed Alberta Innovates Health Solutions). The author acknowledges with heartfelt gratitude the essential collaborations from other members of the Inflammation Research Network at the University of Calgary (www.ucalgary.ca/irn/) and in particular, the joint effort by Dr. Eleftherios Diamandis and the members of his laboratory in Toronto (www.acdclab.org/), coordinated originally for KLK-PAR studies by Dr. Katerina Oikonomopoulou (as outlined in her thesis: Oikonomopoulou, 2008), and the members of the Hollenberg laboratory in Calgary, in particular, Dr. M. Saifeddine, who conducted most of the vascular bioassays and many of the calcium signaling assays described in this overview, and Drs. Bahjat Al-Ani, Steve Compton, Kristina Hansen, Koichiro Mihara, and Rithwik Ramachandran, who have been instrumental in elucidating the molecular mechanisms of PAR signaling summarized in this review.

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Article note

This article summarizes information presented as an E.K. Frey-E. Werle Commemorative Gold Medal oration at the 5th International Symposium on Kallikreins and Kallikrein-Related Peptidases, 28 September, 2013, Toronto, Ontario, Canada.

Received: 2014-2-12
Accepted: 2014-4-23
Published Online: 2014-8-6
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
https://doi.org/10.1515/hsz-2014-0123
Keywords for this article
inflammation; prostate-specific antigen (PSA); protease-activated receptors; proteinase-activated receptors (PARs); signal transduction

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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