Protease Crosstalk with Integrins: the Urokinase Receptor Paradigm
Harold A. Chapman, Ying Wie
Pulmonary and Critical Care Division, University of California at San Francisco, San Francisco, CA, USA
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.