Urokinase receptor

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PLAUR
Protein PLAUR PDB 1YWH.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases PLAUR, CD87, U-PAR, UPAR, URKR, plasminogen activator, urokinase receptor
External IDs OMIM: 173391 MGI: 97612 HomoloGene: 48120 GeneCards: PLAUR
Gene location (Human)
Chromosome 19 (human)
Chr. Chromosome 19 (human)[1]
Chromosome 19 (human)
Genomic location for PLAUR
Genomic location for PLAUR
Band 19q13.31 Start 43,646,095 bp[1]
End 43,670,547 bp[1]
RNA expression pattern
PBB GE PLAUR 210845 s at fs.png

PBB GE PLAUR 211924 s at fs.png

PBB GE PLAUR 214866 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001005376
NM_001005377
NM_001301037
NM_002659

NM_011113

RefSeq (protein)

NP_001005376
NP_001005377
NP_001287966
NP_002650

NP_035243

Location (UCSC) Chr 19: 43.65 – 43.67 Mb Chr 19: 24.46 – 24.48 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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[5] and with its native ligand, urokinase.[6]

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.[7]

Interactions[edit]

Urokinase receptor has been shown to interact with LRP1.[8]

See also[edit]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000011422 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000046223 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ Llinas P, Le Du MH, Gårdsvoll H, Danø K, Ploug M, Gilquin B, Stura EA, Ménez A (May 2005). "Crystal structure of the human urokinase plasminogen activator receptor bound to an antagonist peptide". The EMBO Journal. 24 (9): 1655–63. doi:10.1038/sj.emboj.7600635. PMC 1142576Freely accessible. PMID 15861141. 
  6. ^ 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 (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. 
  7. ^ Thunø M, Macho B, Eugen-Olsen J (2009). "suPAR: the molecular crystal ball". Disease Markers. 27 (3): 157–72. doi:10.3233/DMA-2009-0657. PMID 19893210. 
  8. ^ 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". Molecular Biology of the Cell. 12 (5): 1467–79. doi:10.1091/mbc.12.5.1467. PMC 34598Freely accessible. PMID 11359936. 

Further reading[edit]

External links[edit]