The Urokinase receptor, also known as urokinase plasminogen activator surface receptor (uPAR) or CD87 (Cluster of Differentiation 87), is a protein encoded in humans by the PLAUR gene. It is a multidomain

glycoprotein Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

tethered to the cell membrane with a (GPI) anchor. uPAR was originally identified as a saturable binding site for urokinase (also known as uPA) on the cell surface.

Molecular characteristics

uPAR consists of three tandem LU domains, which are protein domains of the three-finger protein family. The structure of uPAR has been solved by X-ray crystallography in complex with a peptide

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

and with its native ligand, urokinase. All three three-finger domains are necessary for high affinity binding of the primary ligand, urokinase. In addition, uPAR also interacts with several other proteins, including vitronectin, the uPAR associated protein ( uPARAP) and the integrin family of

membrane proteins Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...

. 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 Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not al ...

sites are used in vivo giving the protein a molecular weight of 50-60 kDA.

Physiological significance

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, the old tissue must be able to be degraded. An important mechanism in this degradation is the

proteolysis Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called protease ...

cascade initiated by the plasminogen activation system. uPAR binds urokinase and thus restricts plasminogen activation to the immediate vicinity of the cell membrane. When urokinase is bound to the receptor, there is cleavage between the GPI-anchor and the uPAR, releasing a soluble form of the protein known as

suPAR Soluble urokinase plasminogen activator receptor (suPAR) (NCBI Accession no. AAK31795) is a protein and the soluble form of uPAR. uPAR is expressed mainly on immune cells, endothelial cells, and smooth muscle cells. uPAR is a membrane-bound rece ...

Clinical significance

Soluble urokinase plasminogen activator receptor (suPAR) has been found to be a biomarker of inflammation. Elevated suPAR is seen in chronic obstructive pulmonary disease, asthma, liver failure,

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...

, and rheumatoid arthritis. Smokers have significantly higher suPAR compared to non-smokers. Urokinase receptors have been found to be highly expressed on senescent cells, leading researchers to use chimeric antigen receptor T cells to eliminate senescent cells in mice. 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

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

s of the various components of the plasminogen activation system have been sought as possible anticancer drugs. uPAR has been involved in various other non-proteolytic processes related to cancer, such as cell migration, cell cycle regulation, and cell adhesion.

Molecular characteristics

Physiological significance

Clinical significance

Interactions

See also

References

Further reading

External links