uPAR-uPA-PAI-1 interactions and signaling: a vascular biologist's view.
The urokinase-type plasminogen activator (uPA), its inhibitor PAI-1 and its cellular receptor (uPAR), play a pivotal role in pericellular proteolysis. In addition, through their interactions with extracellular matrix proteins as well as with transmembrane receptors and other links to the intracellular signaling machinery, they modulate cell migration, cell-matrix interactions and signaling pathways. A large body of experimental evidence from in-vitro and in-vivo data as well as from the clinics indicates an important role of the uPA-uPAR-PAI-1 systems in cancer. In addition to their role in tumor cell biology, the uPA-uPAR-PAI-1 systems are also important for vascular biology by modulating angiogenesis and by altering migration of smooth muscle cells and fibrin deposition in atherosclerosis and restenosis. This review will focus on the general mechanism of uPAR/uPA/PAI-1 interactions and signaling and the possible relevance of this system in vascular biology.
Binder
Bernd R
BR
Department of Vascular Biology and Thrombosis Research, Center for Biomolecular Medicine and Pharmacology, Medical University of Vienna, Vienna, Austria. bernd.binder@meduniwien.ac.at
Mihaly
Judit
J
Prager
Gerald W
GW
D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D026502:LDL-Receptor Related Proteins / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D013927:Thrombosis / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D016023:Integrins; D026502:LDL-Receptor Related Proteins; C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D055293:Receptors, Urokinase Plasminogen Activator; D050791:STAT Transcription Factors; D066246:ErbB Receptors; D053612:Janus Kinases; D014568:Urokinase-Type Plasminogen Activator