IMR Press / FBL / Volume 14 / Issue 10 / DOI: 10.2741/3488

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Structure, function and antagonists of urokinase-type plasminogen activator
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1 National Cancer Institute, Via Semmola, Naples
2 Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, National Research Council, Naples
3 Department of Cardio-Thoracic Sciences, Second University of Naples, Naples, Italy
Front. Biosci. (Landmark Ed) 2009, 14(10), 3782–3794;
Published: 1 January 2009

Urokinase (uPA) is a serine protease which converts plasminogen to plasmin, a broad-spectrum protease active on extracellular matrix (ECM) components. Like many components of the blood coagulation, fibrinolytic and complement cascades, uPA has a modular structure, including three conserved domains: a growth factor-like domain (GFD, residues 1 – 49), a kringle domain (residues 50 – 131), linked by an interdomain linker or "connecting peptide" (CP, residues 132 – 158) to the serine protease domain (residues 159 – 411). Although direct molecular interactions with urokinase receptor and integrins have been extensively described, the function of single uPA domains is not completely understood. Because of the causal involvment of uPA in cancer invasion and metastasis, the blockade of uPA interactions and activity with specific inhibitors is of interest for novel strategies in cancer therapy. New inhibitors derived from the interdomain linker or "connecting peptide" are coming into focus. This review summarizes the recent findings on the uPA structure-function relationship and provides further information on existing inhibitors of uPA multiple functions.

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