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The Urokinase receptor, also known as uPA receptor or uPAR, is multidomain glycoprotein tethered to the cell membrane with a glycosylphosphotidylinositol (GPI) anchor. uPAR was originally identified as a saturable binding site for urokinase on the cell surface.
Additional recommended knowledge
uPAR consists of three different domains of the Ly-6/uPAR/alpha-neurotoxin family. All three domains are necessary for high affinity binding of the primary ligand, urokinase. It has been possible to express uPAR recombinantly in CHO-cells and S2 cells from [[Drosophila melanogaster]]. 4 out of 5 of the possible glycosylation sites are used in vivo giving the protein a molecular weight of 50-60 kDA. Recently the structure of uPAR was solved by X-ray crystallography in complex with an peptide antagonist and with its native ligand, urokinase.
Besides the primary ligand urokinase, uPAR interacts with several other proteins, among others: vitronectin, the uPAR associated protein (uPARAP) and the integrin family of membrane proteins.
uPAR is a part of the plasminogen activation system, which in the healthy body is involved in tissue reorganization events such as mammary gland involution and wound healing. In order to be able to reorganize tissue it is important, that the old tissue can be degraded. An important mechanism in this degradation is the proteolysis cascade initiated by the plasminogen activation system. uPAR binds urokinase and thus restricts plasminogen activation to the immediate vicinity of the cell membrane. Thus uPAR seems to be an important player in the regulation of this process.
However the components of the plasminogen activation system have been found to be highly expressed in many malignant tumors, indicating that tumors are able to hijack the system, and use it in metastasis. Thus inhibitors of the various components of the plasminogen activation system has been sought as possible anticancer drugs.
uPAR has been involved in various other non-proteolytical processes related to cancer, such as cell migration, cell cycle regulation and cell adhesion.
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Urokinase_receptor". A list of authors is available in Wikipedia.|