The urokinase receptor as an entertainer of signal transduction.
The serine-protease urokinase (uPA) and its specific membrane receptor uPAR controls matrix degradation through the conversion of plasminogen into plasmin and play a crucial role in a number of biological processes including local fibrinolysis, inflammation, angiogenesis, matrix remodelling during wound healing, tumor invasion and metastasis. Most of the cellular responses modulated by the uPA/uPAR system, including migration, cellular adhesion, differentiation, proliferation and apoptosis require transmembrane signaling, which is mediated by direct contacts of uPAR with a variety of extracellular proteins and membrane receptors, such as integrins, EGF receptor, high molecular weight kininogen, caveolin and the G-protein-coupled receptor FPRL1. As a result of these interactions, uPAR activates intracellular signalling molecules such as tyrosine- and serine-protein kinases, Src, focal adhesion kinase (FAK), Rac, extracellular-signal-regulated kinase (ERK)/mitogen- activated protein kinase (MAPK) and JAK/STAT, being part of a large "signalosome" interacting with several molecules on both the outside and inside of the cell. This review is focused on the biochemistry of the pathways affected by uPAR and its partners.
D'Alessio
Silvia
S
Department of Molecular Biology and Functional Genomics, DIBIT, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy. dalessio.silvia@hsr.it
Blasi
Francesco
F
D002118:Calcium / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D009369:Neoplasms / Q000628:therapy; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D015398:Signal Transduction; D019096:Vitronectin / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D055293:Receptors, Urokinase Plasminogen Activator; D019096:Vitronectin; D020741:rho GTP-Binding Proteins; D002118:Calcium