The urokinase receptor (uPAR, CD87) is a glycoprotein , a receptor anchored to the cell membrane with glycosylphosphatidylinositol . Historically, it was discovered as a saturable urokinase binding site on the surface of a cell.
| Urokinase receptor | |||||||||||||
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| , CD87, U-PAR, UPAR, URKR, plasminogen activator, urokinase receptor | |||||||||||||
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Content
Structure
The protein molecule consists of 3 domains of the Ly-6 / uPAR / alpha-neurotoxin family. All three domains are required for high affinity binding to the main ligand urokinase. The protein contains 4 glycosylation sites, mature glycoprotein has a molecular weight of 50-60 kDa. The crystal structure of the protein is known in combination with a peptide receptor antagonist [1] and with the natural ligand urokinase. [2]
In addition to urokinase itself, it binds to other ligands: vitronectin , mannose receptor (uPARAP) and integrins .
Physiological Importance
The urokinase receptor is part of the plasminogen activation system, which in a healthy body is involved in the process of mammary gland involution and in wound healing. Such a reorganization of tissue requires the degradation of old tissue. Degradation of old tissue during proteolysis is activated by plasminogen. The urokinase receptor binds to urokinase, which limits and localizes plasminogen activation.
However, the components of the plasminogen activation system are found with a high level of expression in many malignant tumors, which means metastasis of the tumor. Inhibitors of the plasminogen system are considered as potential anti-cancer agents.
In addition, the urokinase receptor is also involved in non-proteolytic oncological processes, such as cell migration, cell cycle regulation, and cell adhesion.
The binding of urokinase to the receptor can lead to cleavage of the glycosylphosphatidylinositol anchoring the receptor and the release of the free form of the receptor into the bloodstream [3] .
Interactions
The urokinase receptor interacts with LRP1 . [four]
Literature
- Ploug M. Structure-function relationships in the interaction between the urokinase-type plasminogen activator and its receptor (English) // Current Pharmaceutical Design : journal. - 2003. - Vol. 9 , no. 19 . - P. 1499-1528 . - DOI : 10.2174 / 1381612033454630 . - PMID 12871065 .
- Kjøller L. The urokinase plasminogen activator receptor in the regulation of the actin cytoskeleton and cell motility (Eng.) // Biological Chemistry: journal. - 2002 .-- January ( vol. 383 , no. 1 ). - P. 5-19 . - DOI : 10.1515 / BC.2002.002 . - PMID 11928822 .
- Chavakis T., Kanse SM, May AE, Preissner KT Haemostatic factors occupy new territory: the role of the urokinase receptor system and kininogen in inflammation (Eng.) // Biochemical Society Transactions : journal. - 2002 .-- April ( vol. 30 , no. 2 ). - P. 168—173 . - DOI : 10.1042 / BST0300168 . - PMID 12023845 .
- Ploug M., Gårdsvoll H., Jørgensen TJ, Lønborg Hansen L., Danø K. Structural analysis of the interaction between urokinase-type plasminogen activator and its receptor: a potential target for anti-invasive cancer therapy (Eng.) // Biochemical Society Transactions : journal. - 2002 .-- April ( vol. 30 , no. 2 ). - P. 177-183 . - DOI : 10.1042 / BST0300177 . - PMID 12023847 .
- Alfano M., Sidenius N., Blasi F., Poli G. The role of urokinase-type plasminogen activator (uPA) / uPA receptor in HIV-1 infection (Eng.) // Journal of Leukocyte Biology : journal. - 2003 .-- November ( vol. 74 , no. 5 ). - P. 750—756 . - DOI : 10.1189 / jlb.0403176 . - PMID 12960238 .
- Alfano D., Franco P., Vocca I., Gambi N., Pisa V., Mancini A., Caputi M., Carriero MV, Iaccarino I., Stoppelli MP The urokinase plasminogen activator and its receptor: role in cell growth and apoptosis (English) // Thrombosis and Haemostasis : journal. - 2005 .-- February ( vol. 93 , no. 2 ). - P. 205-211 . - DOI : 10.1160 / TH04-09-0592 . - PMID 15711734 .
Notes
- ↑ Llinas P., Le Du MH, Gårdsvoll H., Danø K., Ploug M., Gilquin B., Stura EA, Ménez A. Crystal structure of the human urokinase plasminogen activator receptor bound to an antagonist peptide / / The EMBO Journal : journal. - 2005 .-- May ( vol. 24 , no. 9 ). - P. 1655-1663 . - DOI : 10.1038 / sj.emboj.7600635 . - PMID 15861141 .
- ↑ Huai Q., Mazar AP, Kuo A., Parry GC, Shaw DE, Callahan J., Li Y., Yuan C., Bian C., Chen L., Furie B., Furie BC, Cines DB, Huang M Structure of human urokinase plasminogen activator in complex with its receptor (English) // Science: journal. - 2006 .-- February ( vol. 311 , no. 5761 ). - P. 656-659 . - DOI : 10.1126 / science.1121143 . - PMID 16456079 .
- ↑ Thunø M., Macho B., Eugen-Olsen J. suPAR: the molecular crystal ball (neopr.) // Disease Markers. - 2009. - T. 27 , No. 3 . - S. 157-172 . - DOI : 10.3233 / DMA-2009-0657 . - PMID 19893210 .
- ↑ Czekay RP, Kuemmel TA, Orlando RA, Farquhar MG Direct binding of occupied urokinase receptor (uPAR) to LDL receptor-related protein is required for endocytosis of uPAR and regulation of cell surface urokinase activity (Eng.) // Molecular Biology of the Cell : journal. - 2001 .-- May ( vol. 12 , no. 5 ). - P. 1467-1479 . - DOI : 10.1091 / mbc.12.5.1467 . - PMID 11359936 .