Urokinase receptor

The Urokinase receptor, also known as uPA receptor or uPAR or CD87 (Cluster of Differentiation 87), is multidomain is_associated_with::glycoprotein tethered to the is_associated_with::cell membrane with a glycosylphosphotidylinositol (GPI) anchor. uPAR was originally identified as a saturable binding site for urokinase on the cell surface.

Molecular characteristics
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 is_associated_with::Drosophila melanogaster. 4 out of 5 of the possible is_associated_with::glycosylation sites are used in vivo giving the is_associated_with::protein a is_associated_with::molecular weight of 50-60 kDA. Recently the structure of uPAR was solved by is_associated_with::X-ray crystallography in complex with a is_associated_with::peptide antagonist and with its native ligand, urokinase.

Besides the primary is_associated_with::ligand is_associated_with::urokinase, uPAR interacts with several other is_associated_with::proteins, among others: is_associated_with::vitronectin, the uPAR associated protein (is_associated_with::uPARAP) and the is_associated_with::integrin family of is_associated_with::membrane proteins.

Physiological significance
uPAR is a part of the is_associated_with::plasminogen activation system, which in the healthy body is involved in tissue reorganization events such as is_associated_with::mammary gland involution and is_associated_with::wound healing. In order to be able to reorganize tissue, the old tissue must be able to be degraded. An important mechanism in this degradation is the is_associated_with::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 is_associated_with::malignant is_associated_with::tumors, indicating that tumors are able to hijack the system, and use it in is_associated_with::metastasis. Thus inhibitors of the various components of the plasminogen activation system have been sought as possible anticancer drugs.

uPAR has been involved in various other non-proteolytical processes related to cancer, such as is_associated_with::cell migration, is_associated_with::cell cycle regulation, and cell adhesion.

When uPA is bound to the receptor, there is cleavage between the GPI-anchor and the uPAR, releasing is_associated_with::suPAR.

Interactions
Urokinase receptor has been shown to interact with is_associated_with::LRP1.