title: Structure, function and antagonists of urokinase-type plasminogen activator.
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.
authors.affiliation: National Cancer Institute, Via Semmola, Naples, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Vincenza Carriero
authors.forename: Paola
authors.initials: P
authors.lastname: Franco
authors.forename: Imma
authors.initials: I
authors.lastname: Vocca
authors.forename: Daniela
authors.initials: D
authors.lastname: Alfano
authors.forename: Immacolata
authors.initials: I
authors.lastname: Longanesi-Cattani
authors.forename: Katia
authors.initials: K
authors.lastname: Bifulco
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mancini
authors.forename: Mario
authors.initials: M
authors.lastname: Caputi
authors.forename: Maria Patrizia
authors.initials: MP
authors.lastname: Stoppelli
mesh_terms: D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D018082:Kringles; D008958:Models, Molecular; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D014568:Urokinase-Type Plasminogen Activator