Urokinase receptor

PLAUR
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1YWH, 2FD6, 3BT1, 3BT2, 3U73, 3U74, 2I9B, 4K24, 4QTI
Identifiers
Aliases	PLAUR, CD87, U-PAR, UPAR, URKR, plasminogen activator, urokinase receptor
External IDs	OMIM: 173391 MGI: 97612 HomoloGene: 48120 GeneCards: PLAUR
Gene ontology Molecular function • protein domain specific binding • protein binding • urokinase plasminogen activator receptor activity • enzyme binding • receptor binding • receptor activity Cellular component • integral component of membrane • cell projection • endoplasmic reticulum lumen • endoplasmic reticulum membrane • membrane • focal adhesion • invadopodium membrane • integral component of plasma membrane • extracellular region • cell junction • anchored component of membrane • extracellular exosome • extrinsic component of membrane • plasma membrane Biological process • movement of cell or subcellular component • positive regulation of protein phosphorylation • negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway • fibrinolysis • negative regulation of intrinsic apoptotic signaling pathway • urokinase plasminogen activator signaling pathway • negative regulation of apoptotic process • blood coagulation • attachment of GPI anchor to protein • chemotaxis • positive regulation of release of cytochrome c from mitochondria • positive regulation of DNA binding • positive regulation of epidermal growth factor receptor signaling pathway • regulation of proteolysis • signal transduction Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5329	18793
Ensembl	ENSG00000011422	ENSMUSG00000046223
UniProt	Q03405	P35456
RefSeq (mRNA)	NM_001005376 NM_001005377 NM_001301037 NM_002659	NM_011113
RefSeq (protein)	NP_001005376.1 NP_001005377.1 NP_001287966.1 NP_002650.1	NP_035243.1
Location (UCSC)	Chr 19: 43.65 – 43.67 Mb	Chr 7: 24.46 – 24.48 Mb
PubMed search	[1]	[2]
Wikidata

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The Urokinase receptor, also known as uPA receptor or uPAR or CD87 (Cluster of Differentiation 87), 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.

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 a peptide antagonist^[3] and with its native ligand, urokinase.^[4]

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, the old tissue must be able to 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 have 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.

When uPA is bound to the receptor, there is cleavage between the GPI-anchor and the uPAR, releasing suPAR.^[5]

Interactions

Urokinase receptor has been shown to interact with LRP1.^[6]

See also

• Cancer
• Cluster of differentiation
• Metastasis
• Plasmin
• Plasminogen activation system
• Urokinase
• suPAR

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Llinas P, Le Du MH, Gårdsvoll H, et al. (May 2005). "Crystal structure of the human urokinase plasminogen activator receptor bound to an antagonist peptide". EMBO J. 24 (9): 1655–63. doi:10.1038/sj.emboj.7600635. PMC 1142576. PMID 15861141.
4. Huai Q, Mazar AP, Kuo A, et al. (February 2006). "Structure of human urokinase plasminogen activator in complex with its receptor". Science. 311 (5761): 656–9. doi:10.1126/science.1121143. PMID 16456079.
5. Thunø M, Macho B, Eugen-Olsen J (2009). "suPAR: the molecular crystal ball". Dis. Markers. 27 (3): 157–72. doi:10.3233/DMA-2009-0657. PMID 19893210.
6. Czekay RP, Kuemmel TA, Orlando RA, Farquhar MG (May 2001). "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". Mol. Biol. Cell. 12 (5): 1467–79. doi:10.1091/mbc.12.5.1467. PMC 34598. PMID 11359936.

Further reading

• Ploug M (2003). "Structure-function relationships in the interaction between the urokinase-type plasminogen activator and its receptor". Curr. Pharm. Des. 9 (19): 1499–528. doi:10.2174/1381612033454630. 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. doi:10.1515/BC.2002.002. 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/BST0300168. 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/BST0300177. 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:10.1160/TH04-09-0592. PMID 15711734.

External links

• PLAUR protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)