Structure, function and antagonists of urokinase-type plasminogen activator

Maria Vincenza Carriero, Paola Franco, Imma Vocca, Daniela Alfano, Giuseppina Votta, Immacolata Longanesi-Cattani, Katia Bifulco, Alessandro Mancini, Mario Caputi, Maria Patrizia Stoppelli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)3782-3794
Number of pages13
JournalFrontiers in Bioscience
Volume14
Issue number10
DOIs
Publication statusPublished - Jan 1 2009

Fingerprint

C-Peptide
Urokinase-Type Plasminogen Activator
Serine Proteases
Kringles
Plasminogen
Fibrinolysin
Blood Coagulation
Integrins
Extracellular Matrix
Neoplasms
Intercellular Signaling Peptides and Proteins
Peptide Hydrolases
Molecular interactions
Neoplasm Metastasis
Coagulation
Blood
Therapeutics

Keywords

  • Inhibitors of urokinase
  • Review
  • Serine protease
  • Urokinase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)

Cite this

Carriero, M. V., Franco, P., Vocca, I., Alfano, D., Votta, G., Longanesi-Cattani, I., ... Stoppelli, M. P. (2009). Structure, function and antagonists of urokinase-type plasminogen activator. Frontiers in Bioscience, 14(10), 3782-3794. https://doi.org/10.2735/3488

Structure, function and antagonists of urokinase-type plasminogen activator. / Carriero, Maria Vincenza; Franco, Paola; Vocca, Imma; Alfano, Daniela; Votta, Giuseppina; Longanesi-Cattani, Immacolata; Bifulco, Katia; Mancini, Alessandro; Caputi, Mario; Stoppelli, Maria Patrizia.

In: Frontiers in Bioscience, Vol. 14, No. 10, 01.01.2009, p. 3782-3794.

Research output: Contribution to journalArticle

Carriero, MV, Franco, P, Vocca, I, Alfano, D, Votta, G, Longanesi-Cattani, I, Bifulco, K, Mancini, A, Caputi, M & Stoppelli, MP 2009, 'Structure, function and antagonists of urokinase-type plasminogen activator', Frontiers in Bioscience, vol. 14, no. 10, pp. 3782-3794. https://doi.org/10.2735/3488
Carriero MV, Franco P, Vocca I, Alfano D, Votta G, Longanesi-Cattani I et al. Structure, function and antagonists of urokinase-type plasminogen activator. Frontiers in Bioscience. 2009 Jan 1;14(10):3782-3794. https://doi.org/10.2735/3488
Carriero, Maria Vincenza ; Franco, Paola ; Vocca, Imma ; Alfano, Daniela ; Votta, Giuseppina ; Longanesi-Cattani, Immacolata ; Bifulco, Katia ; Mancini, Alessandro ; Caputi, Mario ; Stoppelli, Maria Patrizia. / Structure, function and antagonists of urokinase-type plasminogen activator. In: Frontiers in Bioscience. 2009 ; Vol. 14, No. 10. pp. 3782-3794.
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