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Urokinase receptor

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Title: Urokinase receptor  
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Subject: LRP1, Clusters of differentiation, UPARAP, Vitronectin, CD1E
Collection: Clusters of Differentiation
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Urokinase receptor

Plasminogen activator, urokinase receptor
Rendering based on PDB .
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols  ; CD87; U-PAR; UPAR; URKR
External IDs ChEMBL: GeneCards:
RNA expression pattern
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

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.

Contents

  • Molecular characteristics 1
  • Physiological significance 2
  • Interactions 3
  • See also 4
  • References 5
  • Further reading 6
  • External links 7

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[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 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

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

See also

References

  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.  
  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.  
  3. ^ Thunø M, Macho B, Eugen-Olsen J (2009). "suPAR: the molecular crystal ball". Dis. Markers 27 (3): 157–72.  
  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.  

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.  
  • Kjøller L (2003). "The urokinase plasminogen activator receptor in the regulation of the actin cytoskeleton and cell motility.". Biol. Chem. 383 (1): 5–19.  
  • 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.  
  • 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.  
  • 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.  
  • 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.  

External links

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