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
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 b1 and b2 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.