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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year


IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

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1437-4315
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Volume 387, Issue 2 (Feb 2006)

Issues

Interplay of human tissue kallikrein 4 (hK4) with the plasminogen activation system: hK4 regulates the structure and functions of the urokinase-type plasminogen activator receptor (uPAR)

Nathalie Beaufort
  • Unité de Défense Innée et Inflammation/INSERM E0336, Département de Médecine Moléculaire, Institut Pasteur, F-75015 Paris, France and Klinische Forschergruppe der Frauenklinik der Technischen Universität München, D-81675 München, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mekdes Debela
  • Klinische Forschergruppe der Frauenklinik der Technischen Universität München, D-81675 München, Germany and Abteilung Strukturforschung, Max-Planck-Institut für Biochemie, D-82152 Martinsried, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Sabine Creutzburg
  • Klinische Forschergruppe der Frauenklinik der Technischen Universität München, D-81675 München, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Josef Kellermann / Wolfram Bode
  • Abteilung Strukturforschung, Max-Planck-Institut für Biochemie, D-82152 Martinsried, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Manfred Schmitt
  • Klinische Forschergruppe der Frauenklinik der Technischen Universität München, D-81675 München, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Dominique Pidard
  • Unité de Défense Innée et Inflammation/INSERM E0336, Département de Médecine Moléculaire, Institut Pasteur, F-75015 Paris, France
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Viktor Magdolen
  • Klinische Forschergruppe der Frauenklinik der Technischen Universität München, D-81675 München, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2006-02-09 | DOI: https://doi.org/10.1515/BC.2006.029

Abstract

The plasminogen activation system is involved in cancer progression and metastasis. Among other proteolytic factors, it includes the serine protease urokinase-type plasminogen activator (uPA) and its three-domain (D1D2D3) receptor uPAR (CD87), which focuses plasminogen activation to the cell surface. The function of uPAR is regulated in part through shedding of domain D1 by proteases, e.g., uPA itself or plasmin. Human tissue kallikrein 4 (hK4), which is highly expressed in prostate and ovarian tumor tissue, was previously shown to cleave and activate the pro-enzyme forms of prostate-specific antigen (PSA, tissue kallikrein hK3) and uPA. Here we demonstrate that uPAR is also a target for hK4, being cleaved in the D1-D2 linker sequence and, to a lesser extent, in its D3 juxtamembrane domain. hK4 may thus modulate the tumor-associated uPA/uPAR-system activity by either activating the pro-enzyme form of uPA or cleaving the cell surface-associated uPA receptor.

Keywords: enamel matrix serine protease 1; invasion; metastasis; prostase; tumor-associated proteolytic system

About the article

Corresponding author


Received: August 14, 2005

Accepted: October 20, 2005

Published Online: 2006-02-09

Published in Print: 2006-02-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2006.029.

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