Protease crosstalk with integrins: the urokinase receptor paradigm

Thromb Haemost. 2001 Jul;86(1):124-9.

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.

Publication types

  • Review

MeSH terms

  • 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

Substances

  • Integrins
  • PLAUR protein, human
  • Receptors, Cell Surface
  • Receptors, Urokinase Plasminogen Activator
  • Endopeptidases