title: Protease crosstalk with integrins: the urokinase receptor paradigm.
abstract: 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.
authors.affiliation: Pulmonary and Critical Care Division, University of California at San Francisco, 94143-0130, USA. halchap@itsa.ucsf.edu
authors.forename: H A
authors.initials: HA
authors.lastname: Chapman
authors.forename: Y
authors.initials: Y
authors.lastname: Wei
mesh_terms: D010450:Endopeptidases / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D021962:Membrane Microdomains / Q000502:physiology; D020239:Receptor Cross-Talk / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology; D055293:Receptors, Urokinase Plasminogen Activator; D015398:Signal Transduction
chemical_list: D016023:Integrins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010450:Endopeptidases