Summary

Migratory cells use both adhesion receptors and proteolytic enzymesto 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 theintracellular cytoskeleton. One protease system intimately connected tointegrins is the urokinase/urokinase receptor(uPAR)/plasmin system.Recent studies indicate urokinase promotes the ligand-like binding ofits receptor to a set of b₁ and b₂ integrins, this binding in turn affectingintegrin signaling and cell migration. The glycolipid anchor of uPARassociates with cholesterol-rich membrane rafts. Binding of uPAR tointegrins may enrich integrin clusters with signaling molecules such assrc-family kinases that localize to rafts and are important to integrinfunction. Signals derived from integrin/uPAR complexes promote thefunction of other integrins. Thus the urokinase/plasmin system coordinateswith integrins to regulate cell: matrix interactions.