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Urokinase receptor




Plasminogen activator, urokinase receptor
Available structures: 1ywh, 2fd6, 2i9b
Identifiers
Symbol(s) PLAUR; CD87; UPAR; URKR
External IDs OMIM: 173391 MGI: 97612 Homologene: 48120
RNA expression pattern

More reference expression data

Orthologs
Human Mouse
Entrez 5329 18793
Ensembl ENSG00000011422 ENSMUSG00000046223
Uniprot Q03405 Q3U2D1
Refseq NM_001005376 (mRNA)
NP_001005376 (protein) 		NM_011113 (mRNA)
NP_035243 (protein)
Location Chr 19: 48.84 - 48.87 Mb Chr 7: 24.17 - 24.18 Mb
Pubmed search [1] [2]

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.

Contents

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 [[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[1] and with its native ligand, urokinase[2].

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.

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 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.

See also

References

  1. ^ Crystal structure of the human urokinase plasminogen activator receptor bound to an antagonist peptide. Llinas P, Le Du MH, Gardsvoll H, Dano K, Ploug M, Gilquin B, Stura EA, Menez A. EMBO J. 2005 May 4;24(9):1655-63. Epub 2005 Apr 7. (full text article online: Entrez PubMed 15861141).
  2. ^ Structure of human urokinase plasminogen activator in complex with its receptor. 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., Science. 2006 Feb 3;311(5761):656-9. Entrez PubMed 16456079).

Further reading

  • Structure-Function Relationships in the Interaction Between the Urokinase-Type Plasminogen Activator and its Receptor. Ploug, M. Curr Pharm Des. 2003;9(19):1499-528. PMID 12871065.
  • Kjøller L (2003). "The urokinase plasminogen activator receptor in the regulation of the actin cytoskeleton and cell motility.". Biol. Chem. 383 (1): 5-19. PMID 11928822.
  • Chavakis T, Kanse SM, May AE, Preissner KT (2002). "Haemostatic factors occupy new territory: the role of the urokinase receptor system and kininogen in inflammation.". Biochem. Soc. Trans. 30 (2): 168-73. doi:10.1042/. PMID 12023845.
  • Ploug M, Gårdsvoll H, Jørgensen TJ, et al. (2002). "Structural analysis of the interaction between urokinase-type plasminogen activator and its receptor: a potential target for anti-invasive cancer therapy.". Biochem. Soc. Trans. 30 (2): 177-83. doi:10.1042/. PMID 12023847.
  • Alfano M, Sidenius N, Blasi F, Poli G (2004). "The role of urokinase-type plasminogen activator (uPA)/uPA receptor in HIV-1 infection.". J. Leukoc. Biol. 74 (5): 750-6. doi:10.1189/jlb.0403176. PMID 12960238.
  • Alfano D, Franco P, Vocca I, et al. (2005). "The urokinase plasminogen activator and its receptor: role in cell growth and apoptosis.". Thromb. Haemost. 93 (2): 205-11. doi:10.1267/THRO05020205. PMID 15711734.
 
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.
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