The urokinase receptor (uPAR) and the uPAR-associated protein (uPARAP/Endo180): membrane proteins engaged in matrix turnover during tissue remodeling.
The breakdown of the barriers formed by extracellular matrix proteins is a pre-requisite for all processes of tissue remodeling. Matrix degradation reactions take part in specific physiological events in the healthy organism but also represent a crucial step in cancer invasion. These degradation processes involve a highly organized interplay between proteases and their cellular binding sites as well as specific substrates and internalization receptors. This review article is focused on two components, the urokinase plasminogen activator receptor (uPAR) and the uPAR-associated protein (uPARAP, also designated Endo180), that are considered crucially engaged in matrix degradation. uPAR and uPARAP have highly diverse functions, but on certain cell types they interact with each other in a process that is still incompletely understood. uPAR is a glycosyl-phosphatidylinositol-anchored glycoprotein on the surface of various cell types that serves to bind the urokinase plasminogen activator and localize the activation reactions in the proteolytic cascade system of plasminogen activation. uPARAP is an integral membrane protein with a pronounced role in the internalization of collagen for intracellular degradation. Both receptors have additional functions that are currently being unraveled. The present discussion of uPAR and uPARAP is centered on their protein structure and molecular and cellular function.
Behrendt
Niels
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Finsen Laboratory, Rigshospitalet, Strandboulevarden 49, Bldg. 7.2, DK-2100 Copenhagen O, Denmark.
D000818:Animals; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology; D008958:Models, Molecular; D009369:Neoplasms / Q000378:metabolism; D010958:Plasminogen / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011975:Receptors, Mitogen / Q000737:chemistry / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D015398:Signal Transduction / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000378:metabolism
C408294:Endo180; D008562:Membrane Glycoproteins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D011975:Receptors, Mitogen; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen; D003094:Collagen; D014568:Urokinase-Type Plasminogen Activator