Regulation of cell signalling by uPAR

HW Smith, CJ Marshall - Nature reviews Molecular cell biology, 2010 - nature.com
HW Smith, CJ Marshall
Nature reviews Molecular cell biology, 2010nature.com
Urokinase-type plasminogen activator receptor (uPAR) expression is elevated during
inflammation and tissue remodelling and in many human cancers, in which it frequently
indicates poor prognosis. uPAR regulates proteolysis by binding the extracellular protease
urokinase-type plasminogen activator (uPA; also known as urokinase) and also activates
many intracellular signalling pathways. Coordination of extracellular matrix (ECM)
proteolysis and cell signalling by uPAR underlies its important function in cell migration …
Abstract
Urokinase-type plasminogen activator receptor (uPAR) expression is elevated during inflammation and tissue remodelling and in many human cancers, in which it frequently indicates poor prognosis. uPAR regulates proteolysis by binding the extracellular protease urokinase-type plasminogen activator (uPA; also known as urokinase) and also activates many intracellular signalling pathways. Coordination of extracellular matrix (ECM) proteolysis and cell signalling by uPAR underlies its important function in cell migration, proliferation and survival and makes it an attractive therapeutic target in cancer and inflammatory diseases. uPAR lacks transmembrane and intracellular domains and so requires transmembrane co-receptors for signalling. Integrins are essential uPAR signalling co-receptors and a second uPAR ligand, the ECM protein vitronectin, is also crucial for this process.
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