Urokinase receptor

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Plasminogen activator, urokinase receptor
Protein PLAUR PDB 1YWH.png
Rendering based on PDB 1YWH.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PLAUR ; CD87; U-PAR; UPAR; URKR
External IDs OMIM173391 MGI97612 HomoloGene48120 ChEMBL: 4883 GeneCards: PLAUR Gene
RNA expression pattern
PBB GE PLAUR 210845 s at tn.png
PBB GE PLAUR 211924 s at tn.png
PBB GE PLAUR 214866 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5329 18793
Ensembl ENSG00000011422 ENSMUSG00000046223
UniProt Q03405 P35456
RefSeq (mRNA) NM_001005376 NM_011113
RefSeq (protein) NP_001005376 NP_035243
Location (UCSC) Chr 19:
44.15 – 44.17 Mb
Chr 7:
24.46 – 24.48 Mb
PubMed search [1] [2]

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[edit]

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[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[edit]

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.[3]

Interactions[edit]

Urokinase receptor has been shown to interact with LRP1.[4]

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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[edit]

External links[edit]