The Urokinase receptor, also known as urokinase plasminogen activator surface receptor (uPAR) or CD87 (Cluster of Differentiation 87), is a protein encoded in humans by the PLAURgene. It is a multidomainglycoprotein tethered to the cell membrane with a glycosylphosphotidylinositol (GPI) anchor. uPAR was originally identified as a saturable binding site for urokinase (also known as uPA) on the cell surface.
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. When urokinase is bound to the receptor, there is cleavage between the GPI-anchor and the uPAR, releasing a soluble form of the protein known as suPAR.[8][9]
The components of the plasminogen activation system have been found to be highly expressed in many malignanttumors, 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.[13]
uPAR has been involved in various other non-proteolytic processes related to cancer, such as cell migration, cell cycle regulation, and cell adhesion.
^ abcGRCh38: Ensembl release 89: ENSG00000011422 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000046223 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Kessler, Pascal; Marchot, Pascale; Silva, Marcela; Servent, Denis (August 2017). "The three-finger toxin fold: a multifunctional structural scaffold able to modulate cholinergic functions". Journal of Neurochemistry. 142: 7–18. doi:10.1111/jnc.13975. PMID 28326549.
^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. PMC1142576. PMID 15861141.
^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. Bibcode:2006Sci...311..656H. doi:10.1126/science.1121143. PMID 16456079. S2CID 39521660.
^ViroGates. "What is suPAR". suPARnostic® by ViroGates. Retrieved 2021-09-27.
^Josip Madunić (2018). "The Urokinase Plasminogen Activator System in Human Cancers: An Overview of Its Prognostic and Predictive Role". Thrombosis and Haemostasis. 118 (12): 2020–2036. doi:10.1055/s-0038-1675399. PMID 30419600.
^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. PMC34598. PMID 11359936.
Further readingedit
Ploug M (2003). "Structure-function relationships in the interaction between the urokinase-type plasminogen activator and its receptor". Current Pharmaceutical Design. 9 (19): 1499–528. doi:10.2174/1381612033454630. PMID 12871065.
Kjøller L (January 2002). "The urokinase plasminogen activator receptor in the regulation of the actin cytoskeleton and cell motility". Biological Chemistry. 383 (1): 5–19. doi:10.1515/BC.2002.002. PMID 11928822. S2CID 6125978.
Chavakis T, Kanse SM, May AE, Preissner KT (April 2002). "Haemostatic factors occupy new territory: the role of the urokinase receptor system and kininogen in inflammation". Biochemical Society Transactions. 30 (2): 168–73. doi:10.1042/BST0300168. PMID 12023845.
Ploug M, Gårdsvoll H, Jørgensen TJ, Lønborg Hansen L, Danø K (April 2002). "Structural analysis of the interaction between urokinase-type plasminogen activator and its receptor: a potential target for anti-invasive cancer therapy". Biochemical Society Transactions. 30 (2): 177–83. doi:10.1042/BST0300177. PMID 12023847.
Alfano M, Sidenius N, Blasi F, Poli G (November 2003). "The role of urokinase-type plasminogen activator (uPA)/uPA receptor in HIV-1 infection". Journal of Leukocyte Biology. 74 (5): 750–6. doi:10.1189/jlb.0403176. PMID 12960238. S2CID 8526093.
Alfano D, Franco P, Vocca I, Gambi N, Pisa V, Mancini A, Caputi M, Carriero MV, Iaccarino I, Stoppelli MP (February 2005). "The urokinase plasminogen activator and its receptor: role in cell growth and apoptosis". Thrombosis and Haemostasis. 93 (2): 205–11. doi:10.1160/TH04-09-0592. PMID 15711734. S2CID 35517406.
Overview of all the structural information available in the PDB for UniProt: Q03405 (Human Urokinase plasminogen activator surface receptor) at the PDBe-KB.
January 01, 1970
urokinase, receptor, also, known, urokinase, plasminogen, activator, surface, receptor, upar, cd87, cluster, differentiation, protein, encoded, humans, plaur, gene, multidomain, glycoprotein, tethered, cell, membrane, with, glycosylphosphotidylinositol, anchor. The Urokinase receptor also known as urokinase plasminogen activator surface receptor uPAR or CD87 Cluster of Differentiation 87 is a protein encoded in humans by the PLAUR gene It is a multidomain glycoprotein tethered to the cell membrane with a glycosylphosphotidylinositol GPI anchor uPAR was originally identified as a saturable binding site for urokinase also known as uPA on the cell surface PLAURAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes1YWH 2FD6 3BT1 3BT2 3U73 3U74 2I9B 4K24 4QTIIdentifiersAliasesPLAUR CD87 U PAR UPAR URKR plasminogen activator urokinase receptorExternal IDsOMIM 173391 MGI 97612 HomoloGene 48120 GeneCards PLAURGene location Human Chr Chromosome 19 human 1 Band19q13 31Start43 646 095 bp 1 End43 670 547 bp 1 Gene location Mouse Chr Chromosome 7 mouse 2 Band7 7 A3Start24 161 909 bp 2 End24 175 393 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inperiodontal fibermonocytestromal cell of endometriumvena cavagallbladderbloodbone marrow cellsright lungupper lobe of left lungpancreatic ductal cellTop expressed inright lung lobebone marrowcalvariamucous cell of stomachspleenleft lung lobebelly cordmorulabloodendocardial cushionMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionprotein domain specific binding protein binding urokinase plasminogen activator receptor activity enzyme binding signaling receptor binding signaling receptor activityCellular componentintegral component of membrane cell projection endoplasmic reticulum lumen endoplasmic reticulum membrane membrane focal adhesion integral component of plasma membrane extracellular region cell junction anchored component of membrane extracellular exosome extrinsic component of membrane plasma membrane specific granule membrane cell surfaceBiological processpositive 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 neutrophil degranulationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez532918793EnsemblENSG00000011422ENSMUSG00000046223UniProtQ03405P35456RefSeq mRNA NM 001005376NM 001005377NM 001301037NM 002659NM 011113RefSeq protein NP 001005376NP 001005377NP 001287966NP 002650NP 035243Location UCSC Chr 19 43 65 43 67 MbChr 7 24 16 24 18 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Molecular characteristics 2 Physiological significance 3 Clinical significance 4 Interactions 5 See also 6 References 7 Further reading 8 External linksMolecular characteristics edituPAR consists of three tandem LU domains which are protein domains of the three finger protein family 5 The structure of uPAR has been solved by X ray crystallography in complex with a peptide antagonist 6 and with its native ligand urokinase 7 All three three finger domains are necessary for high affinity binding of the primary ligand urokinase In addition uPAR also interacts with several other proteins including vitronectin the uPAR associated protein uPARAP and the integrin family of membrane proteins 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 Physiological significance edituPAR 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 When urokinase is bound to the receptor there is cleavage between the GPI anchor and the uPAR releasing a soluble form of the protein known as suPAR 8 9 Clinical significance editSoluble urokinase plasminogen activator receptor suPAR has been found to be a biomarker of inflammation 10 Elevated suPAR is seen in chronic obstructive pulmonary disease asthma liver failure heart failure cardiovascular disease and rheumatoid arthritis 10 Smokers have significantly higher suPAR compared to non smokers 10 Urokinase receptors have been found to be highly expressed on senescent cells leading researchers to use chimeric antigen receptor T cells to eliminate senescent cells in mice 11 12 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 13 uPAR has been involved in various other non proteolytic processes related to cancer such as cell migration cell cycle regulation and cell adhesion Interactions editUrokinase receptor has been shown to interact with LRP1 14 See also editCancer Cluster of differentiation Metastasis Plasmin suPAR UrokinaseReferences edit a b c GRCh38 Ensembl release 89 ENSG00000011422 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000046223 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Kessler Pascal Marchot Pascale Silva Marcela Servent Denis August 2017 The three finger toxin fold a multifunctional structural scaffold able to modulate cholinergic functions Journal of Neurochemistry 142 7 18 doi 10 1111 jnc 13975 PMID 28326549 Llinas P Le Du MH Gardsvoll H Dano K Ploug M Gilquin B Stura EA Menez 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 1142576 PMID 15861141 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 Bibcode 2006Sci 311 656H doi 10 1126 science 1121143 PMID 16456079 S2CID 39521660 ViroGates What is suPAR suPARnostic by ViroGates Retrieved 2021 09 27 Thuno M Macho B Eugen Olsen J 2009 suPAR the molecular crystal ball Disease Markers 27 3 157 72 doi 10 1155 2009 504294 PMC 3835059 PMID 19893210 a b c Desmedt S Desmedt V Delanghe JR Speeckaert R Speeckaert MM 2017 The Intriguing Role of Soluble Urokinase Receptor in Inflammatory Diseases Critical Reviews in Clinical Laboratory Sciences 54 2 117 133 doi 10 1080 10408363 2016 1269310 PMID 28084848 S2CID 32624995 Wagner V Gil J 2020 T Cells Engineered to Target Senescence Nature 583 7814 37 38 Bibcode 2020Natur 583 37W doi 10 1038 d41586 020 01759 x hdl 10044 1 80980 PMID 32601490 Amor C Feucht J Lowe SW 2020 Senolytic CAR T cells reverse senescence associated pathologies Nature 583 7814 127 132 doi 10 1038 s41586 020 2403 9 PMC 7583560 PMID 32555459 Josip Madunic 2018 The Urokinase Plasminogen Activator System in Human Cancers An Overview of Its Prognostic and Predictive Role Thrombosis and Haemostasis 118 12 2020 2036 doi 10 1055 s 0038 1675399 PMID 30419600 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 34598 PMID 11359936 Further reading editPloug M 2003 Structure function relationships in the interaction between the urokinase type plasminogen activator and its receptor Current Pharmaceutical Design 9 19 1499 528 doi 10 2174 1381612033454630 PMID 12871065 Kjoller L January 2002 The urokinase plasminogen activator receptor in the regulation of the actin cytoskeleton and cell motility Biological Chemistry 383 1 5 19 doi 10 1515 BC 2002 002 PMID 11928822 S2CID 6125978 Chavakis T Kanse SM May AE Preissner KT April 2002 Haemostatic factors occupy new territory the role of the urokinase receptor system and kininogen in inflammation Biochemical Society Transactions 30 2 168 73 doi 10 1042 BST0300168 PMID 12023845 Ploug M Gardsvoll H Jorgensen TJ Lonborg Hansen L Dano K April 2002 Structural analysis of the interaction between urokinase type plasminogen activator and its receptor a potential target for anti invasive cancer therapy Biochemical Society Transactions 30 2 177 83 doi 10 1042 BST0300177 PMID 12023847 Alfano M Sidenius N Blasi F Poli G November 2003 The role of urokinase type plasminogen activator uPA uPA receptor in HIV 1 infection Journal of Leukocyte Biology 74 5 750 6 doi 10 1189 jlb 0403176 PMID 12960238 S2CID 8526093 Alfano D Franco P Vocca I Gambi N Pisa V Mancini A Caputi M Carriero MV Iaccarino I Stoppelli MP February 2005 The urokinase plasminogen activator and its receptor role in cell growth and apoptosis Thrombosis and Haemostasis 93 2 205 11 doi 10 1160 TH04 09 0592 PMID 15711734 S2CID 35517406 External links editPLAUR protein human at the U S National Library of Medicine Medical Subject Headings MeSH Overview of all the structural information available in the PDB for UniProt Q03405 Human Urokinase plasminogen activator surface receptor at the PDBe KB Retrieved from https en wikipedia org w index php title Urokinase receptor amp oldid 1188101336, wikipedia, wiki, book, books, library,
