Protease crosstalk with integrins: the urokinase receptor paradigm

• Published in: Thrombosis and haemostasis Vol. 86; no. 1; p. 124
• Main Authors: Chapman, H A, Wei, Y
• Format: Journal Article
• Language: English
• Published: Germany 01.07.2001
• Subjects: Endopeptidases - metabolism; Endopeptidases - physiology; Humans; Integrins - metabolism; Integrins - physiology; Membrane Microdomains - physiology; Receptor Cross-Talk - physiology; Receptors, Cell Surface - metabolism; Receptors, Cell Surface - physiology; Receptors, Urokinase Plasminogen Activator; Signal Transduction
• ISSN: 0340-6245
• DOI: 10.1055/s-0037-1616208

Migratory cells use both adhesion receptors and proteolytic enzymes to regulate their interaction with and response to extracellular matrices. Cooperation between integrins and proteases operates at several levels: integrin signaling induces proteases, proteases co-localize with integrins, and proteases regulate the interface between integrins and the intracellular cytoskeleton. One protease system intimately connected to integrins is the urokinase/urokinase receptor(uPAR)/plasmin system. Recent studies indicate urokinase promotes the ligand-like binding of its receptor to a set of beta1 and beta2 integrins, this binding in turn affecting integrin signaling and cell migration. The glycolipid anchor of uPAR associates with cholesterol-rich membrane rafts. Binding of uPAR to integrins may enrich integrin clusters with signaling molecules such as src-family kinases that localize to rafts and are important to integrin function. Signals derived from integrin/uPAR complexes promote the function of other integrins. Thus the urokinase/plasmin system coordinates with integrins to regulate cell: matrix interactions.