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Gene Review

PLAUR  -  plasminogen activator, urokinase receptor

Homo sapiens

Synonyms: CD87, MO3, Monocyte activation antigen Mo3, U-PAR, UPAR, ...
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Disease relevance of PLAUR


Psychiatry related information on PLAUR


High impact information on PLAUR

  • We concluded that breaching of the vascular wall is a rate-limiting step for intravasation, and consequently for metastasis, and that cooperation between uPA/uPAR and MMP-9 is required to complete this step [9].
  • Individual development and uPA-receptor expression of disseminated tumour cells in bone marrow: a reference to early systemic disease in solid cancer [10].
  • The urokinase-type plasminogen activator receptor (uPAR) and integrins formed stable complexes that both inhibited native integrin adhesive function and promoted adhesion to vitronectin via a ligand binding site on uPAR [11].
  • Both uPAR-mediated adhesion and altered integrin function were blocked by a peptide that bound to uPAR and disrupted complexes [11].
  • Results obtained recently have led to new insights into the structural aspects of uPAR interaction with integrins, provided a more detailed description of the signaling pathway they induce, and determined that uPAR signaling plays a role in cell migration and tumorigenicity [12].

Chemical compound and disease context of PLAUR


Biological context of PLAUR


Anatomical context of PLAUR

  • The cell hybrid study suggested that PLAUR is located at chromosome 19q13-qter, and the multipoint analysis indicated that PLAUR is located at chromosome 19q13.1-q13.2 and surrounded by DNA markers in the following way (with distances given in recombination fractions): D19S27-.11-CYP2A-.06-PLAUR-.03-D19S8-.04-APOC 2-.24-PRKCG [18].
  • In a uPAR-deficient cell line (LM-TK-), suPAR increased uPA binding up to 10-fold, whereas the truncated receptor lacking the amino-terminal uPA-binding domain was ineffective [22].
  • In conclusion, we found that uPAR expression is elevated on monocytes in AMI and contributes to enhanced cell adhesion [23].
  • In this study, we used human peripheral blood neutrophils and transfected cells expressing alpha(M)beta(2), uPAR, or both receptors to show that the integrin can directly interact with urokinase (uPA) [24].
  • Previous studies demonstrated that integrin alpha(M)beta(2) (CD11b/18, Mac-1) forms a physical complex with the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes [24].

Associations of PLAUR with chemical compounds

  • Direct binding and regulation of alpha5beta1 by uPAR implies a modified "bent" integrin conformation can function in an alternative activation state with this and possibly other cis-acting membrane ligands [25].
  • Using recombinant proteins, we found uPAR directly binds alpha5beta1 and rather than blocking, renders fibronectin (Fn) binding by alpha5beta1 Arg-Gly-Asp (RGD) resistant [25].
  • Saturation of uPAR with urokinase also inhibited binding of the procoagulant Mac-1 ligand, Factor X [26].
  • Induction of Mac-1 and uPAR expression on monocytic cell lines by transforming growth factor- beta 1 and 1.25-(OH)2 vitamin D3 conferred urokinase and uPAR-dependent adhesion to vitronectin, which was further promoted by engagement of Mac-1 [26].
  • We conclude that VEGF165 induces u-PAR via a PKC-dependent pathway, whereas proliferation is induced via a different pathway probably involving tyrosine phosphorylation of proteins downstream of the VEGF receptors [27].
  • The data indicate a dual role for caveolin-1 in the uPAR signaling pathway, leading to integrin activation [28].

Physical interactions of PLAUR

  • Thus, recognition of uPA by alpha(M)beta(2) allows for formation of a multicontact trimolecular complex, in which a single uPA ligand may bind simultaneously to both uPAR and alpha(M)beta(2) [24].
  • This is taken as evidence for mediation of internalization and degradation of uPAR-bound uPA.PAI-1 by alpha 2MR/LRP [29].
  • Both receptors promote degradation of fibrin(ogen) and also confer adhesive properties on cells because Mac-1 and uPAR bind fibrin and vitronectin, respectively [26].
  • At 4 degrees C, both uPA/PAI-2 complex degradation products remain bound to the uPA-R [30].
  • Coimmunoprecipitation assays revealed that soluble recombinant uPAR (suPAR) bound the Man-6-P/IGF2R at two distinct sites, one localized to the amino-terminal end of the Man-6-P/IGF2R extracytoplasmic domain (repeats 1-3) and the other to the more carboxyl-terminal end (repeats 7-9) [31].

Enzymatic interactions of PLAUR

  • The urokinase-type plasminogen activator (uPA) is able to cleave its cell surface receptor (uPAR) anchored to the cell membrane through a glycophosphatidylinositol tail [32].

Co-localisations of PLAUR

  • CK2 localization at the cell surface was highly dynamic; Vn induced formation of clusters where CK2 colocalized with uPAR and alpha(v)beta(3) integrins [33].
  • With this technique uPAR colocalizes with uPA in 71% of labeled granules [34].
  • Indirect immunofluorescence with anti-uPAR antibodies on the melanoma cells showed a punctated staining pattern that accumulated to stretches along sides of cell-cell contact and membrane ruffles. uPAR colocalized with caveolin, a characteristic protein in the coat of caveolae, as demonstrated by double staining with specific antibodies [35].
  • We used laser scanning and immunoelectron microscopy studies to further demonstrate that nucleolin and casein kinase 2 are located on the cell surface where they colocalize with the uPAR [36].

Regulatory relationships of PLAUR


Other interactions of PLAUR

  • This function of uPAR is not dependent upon its occupancy with uPA, which negatively influences adhesion [40].
  • These findings provide a molecular basis for mechanisms VSMC use to induce uPAR- and PDGFR-directed signaling [41].
  • Thus, VN-mediated uPA binding to cells was regulated by the ratio of soluble to surface-associated uPAR [22].
  • In competitive inhibition experiments, anti-CK1, anti-uPAR, or anti-gC1qR blocked both biotin-HK binding and prekallikrein (PK) activation on HUVECs with an inhibitory concentration of 50% (IC(50)) of 300 to 350 nM, 50 to 60 nM, or 35 to 100 nM, respectively [42].
  • Low-density lipoprotein receptor-related protein (LRP) mediates internalization of urokinase:plasminogen activator inhibitor complexes (uPA:PAI-1) and the urokinase receptor (uPAR) [43].
  • Purified p53 protein specifically binds to the uPAR mRNA 3' untranslated region (3'UTR), and endogenous uPAR mRNA associates with p53 [44].

Analytical, diagnostic and therapeutic context of PLAUR


  1. Urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia: implications for capillary-like tube formation in a fibrin matrix. Kroon, M.E., Koolwijk, P., van der Vecht, B., van Hinsbergh, V.W. Blood (2000) [Pubmed]
  2. Urokinase plasminogen activator receptor (uPA-R): one potential characteristic of metastatic phenotypes in minimal residual tumor disease. Allgayer, H., Heiss, M.M., Riesenberg, R., Grützner, K.U., Tarabichi, A., Babic, R., Schildberg, F.W. Cancer Res. (1997) [Pubmed]
  3. Identification of a urokinase receptor-integrin interaction site. Promiscuous regulator of integrin function. Simon, D.I., Wei, Y., Zhang, L., Rao, N.K., Xu, H., Chen, Z., Liu, Q., Rosenberg, S., Chapman, H.A. J. Biol. Chem. (2000) [Pubmed]
  4. The role of urokinase-type plasminogen activator (uPA)/uPA receptor in HIV-1 infection. Alfano, M., Sidenius, N., Blasi, F., Poli, G. J. Leukoc. Biol. (2003) [Pubmed]
  5. uPAR induces epithelial-mesenchymal transition in hypoxic breast cancer cells. Lester, R.D., Jo, M., Montel, V., Takimoto, S., Gonias, S.L. J. Cell Biol. (2007) [Pubmed]
  6. Differential proteome expression associated with urokinase plasminogen activator receptor (uPAR) suppression in malignant epithelial cancer. Saldanha, R.G., Xu, N., Molloy, M.P., Veal, D.A., Baker, M.S. J. Proteome Res. (2008) [Pubmed]
  7. Expression of the urokinase plasminogen activator and its receptor in HIV-1-associated central nervous system disease. Sidenius, N., Nebuloni, M., Sala, S., Zerbi, P., Price, R.W., Gisslen, M., Hagberg, L., Vago, L., Lazzarin, A., Blasi, F., Cinque, P. J. Neuroimmunol. (2004) [Pubmed]
  8. Cortical neurons of Creutzfeldt-Jakob disease patients express the urokinase-type plasminogen activator receptor. Deininger, M.H., Trautmann, K., Magdolen, V., Luther, T., Schluesener, H.J., Meyermann, R. Neurosci. Lett. (2002) [Pubmed]
  9. Requirement for specific proteases in cancer cell intravasation as revealed by a novel semiquantitative PCR-based assay. Kim, J., Yu, W., Kovalski, K., Ossowski, L. Cell (1998) [Pubmed]
  10. Individual development and uPA-receptor expression of disseminated tumour cells in bone marrow: a reference to early systemic disease in solid cancer. Heiss, M.M., Allgayer, H., Gruetzner, K.U., Funke, I., Babic, R., Jauch, K.W., Schildberg, F.W. Nat. Med. (1995) [Pubmed]
  11. Regulation of integrin function by the urokinase receptor. Wei, Y., Lukashev, M., Simon, D.I., Bodary, S.C., Rosenberg, S., Doyle, M.V., Chapman, H.A. Science (1996) [Pubmed]
  12. Urokinase receptor and integrin partnership: coordination of signaling for cell adhesion, migration and growth. Ossowski, L., Aguirre-Ghiso, J.A. Curr. Opin. Cell Biol. (2000) [Pubmed]
  13. Mechanisms of pertussis toxin-induced myelomonocytic cell adhesion: role of Mac-1(CD11b/CD18) and urokinase receptor (CD87). Wong, W.S., Simon, D.I., Rosoff, P.M., Rao, N.K., Chapman, H.A. Immunology (1996) [Pubmed]
  14. Increased metastatic dissemination in human melanoma xenografts after subcurative radiation treatment: radiation-induced increase in fraction of hypoxic cells and hypoxia-induced up-regulation of urokinase-type plasminogen activator receptor. Rofstad, E.K., Mathiesen, B., Galappathi, K. Cancer Res. (2004) [Pubmed]
  15. Lipids isolated from bone induce the migration of human breast cancer cells. Silva, J., Dasgupta, S., Wang, G., Krishnamurthy, K., Ritter, E., Bieberich, E. J. Lipid Res. (2006) [Pubmed]
  16. Aspirin upregulates expression of urokinase type plasminogen activator receptor (uPAR) gene in human colon cancer cells through AP1. Jamaluddin, M.S. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  17. Interleukin-1beta-induced expression of the urokinase-type plasminogen activator receptor and its co-localization with MMPs in human articular chondrocytes. Schwab, W., Schulze-Tanzil, G., Mobasheri, A., Dressler, J., Kotzsch, M., Shakibaei, M. Histol. Histopathol. (2004) [Pubmed]
  18. Assignment of the urokinase-type plasminogen activator receptor gene (PLAUR) to chromosome 19q13.1-q13.2. Børglum, A.D., Byskov, A., Ragno, P., Roldan, A.L., Tripputi, P., Cassani, G., Danø, K., Blasi, F., Bolund, L., Kruse, T.A. Am. J. Hum. Genet. (1992) [Pubmed]
  19. Distinct gene subsets are induced at different time points after human respiratory syncytial virus infection of A549 cells. Martínez, I., Lombardía, L., García-Barreno, B., Domínguez, O., Melero, J.A. J. Gen. Virol. (2007) [Pubmed]
  20. Assignment of the human urokinase receptor gene (PLAUR) to 19q13. Vagnarelli, P., Raimondi, E., Mazzieri, R., De Carli, L., Mignatti, P. Cytogenet. Cell Genet. (1992) [Pubmed]
  21. Is plasminogen activator inhibitor-1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release? Deng, G., Curriden, S.A., Wang, S., Rosenberg, S., Loskutoff, D.J. J. Cell Biol. (1996) [Pubmed]
  22. Vitronectin concentrates proteolytic activity on the cell surface and extracellular matrix by trapping soluble urokinase receptor-urokinase complexes. Chavakis, T., Kanse, S.M., Yutzy, B., Lijnen, H.R., Preissner, K.T. Blood (1998) [Pubmed]
  23. Urokinase receptor surface expression regulates monocyte adhesion in acute myocardial infarction. May, A.E., Schmidt, R., Kanse, S.M., Chavakis, T., Stephens, R.W., Schömig, A., Preissner, K.T., Neumann, F.J. Blood (2002) [Pubmed]
  24. Convergence of the adhesive and fibrinolytic systems: recognition of urokinase by integrin alpha Mbeta 2 as well as by the urokinase receptor regulates cell adhesion and migration. Pluskota, E., Soloviev, D.A., Plow, E.F. Blood (2003) [Pubmed]
  25. Regulation of alpha5beta1 integrin conformation and function by urokinase receptor binding. Wei, Y., Czekay, R.P., Robillard, L., Kugler, M.C., Zhang, F., Kim, K.K., Xiong, J.P., Humphries, M.J., Chapman, H.A. J. Cell Biol. (2005) [Pubmed]
  26. Mac-1 (CD11b/CD18) and the urokinase receptor (CD87) form a functional unit on monocytic cells. Simon, D.I., Rao, N.K., Xu, H., Wei, Y., Majdic, O., Ronne, E., Kobzik, L., Chapman, H.A. Blood (1996) [Pubmed]
  27. Vascular endothelial growth factor enhances the expression of urokinase receptor in human endothelial cells via protein kinase C activation. Kroon, M.E., Koolwijk, P., Vermeer, M.A., van der Vecht, B., van Hinsbergh, V.W. Thromb. Haemost. (2001) [Pubmed]
  28. A dual role for caveolin-1 in the regulation of fibronectin matrix assembly by uPAR. Monaghan-Benson, E., Mastick, C.C., McKeown-Longo, P.J. J. Cell. Sci. (2008) [Pubmed]
  29. Purified alpha 2-macroglobulin receptor/LDL receptor-related protein binds urokinase.plasminogen activator inhibitor type-1 complex. Evidence that the alpha 2-macroglobulin receptor mediates cellular degradation of urokinase receptor-bound complexes. Nykjaer, A., Petersen, C.M., Møller, B., Jensen, P.H., Moestrup, S.K., Holtet, T.L., Etzerodt, M., Thøgersen, H.C., Munch, M., Andreasen, P.A. J. Biol. Chem. (1992) [Pubmed]
  30. Urokinase-type plasminogen activator/type-2 plasminogen-activator inhibitor complexes are not internalized upon binding to the urokinase-type-plasminogen-activator receptor in THP-1 cells. Interaction of urokinase-type plasminogen activator/type-2 plasminogen-activator inhibitor complexes with the cell surface. Ragno, P., Montuori, N., Rossi, G. Eur. J. Biochem. (1995) [Pubmed]
  31. Binding of urokinase-type plasminogen activator receptor (uPAR) to the mannose 6-phosphate/insulin-like growth factor II receptor: contrasting interactions of full-length and soluble forms of uPAR. Kreiling, J.L., Byrd, J.C., Deisz, R.J., Mizukami, I.F., Todd, R.F., MacDonald, R.G. J. Biol. Chem. (2003) [Pubmed]
  32. The cleavage of the urokinase receptor regulates its multiple functions. Montuori, N., Carriero, M.V., Salzano, S., Rossi, G., Ragno, P. J. Biol. Chem. (2002) [Pubmed]
  33. Urokinase-dependent human vascular smooth muscle cell adhesion requires selective vitronectin phosphorylation by ectoprotein kinase CK2. Stepanova, V., Jerke, U., Sagach, V., Lindschau, C., Dietz, R., Haller, H., Dumler, I. J. Biol. Chem. (2002) [Pubmed]
  34. Subcellular distribution of urokinase and urokinase receptor in human neutrophils determined by immunoelectron microscopy. Pedersen, T.L., Plesner, T., Horn, T., Høyer-Hansen, G., Sørensen, S., Hansen, N.E. Ultrastructural pathology. (2000) [Pubmed]
  35. The urokinase-type plasminogen activator receptor, a GPI-linked protein, is localized in caveolae. Stahl, A., Mueller, B.M. J. Cell Biol. (1995) [Pubmed]
  36. Urokinase-induced mitogenesis is mediated by casein kinase 2 and nucleolin. Dumler, I., Stepanova, V., Jerke, U., Mayboroda, O.A., Vogel, F., Bouvet, P., Tkachuk, V., Haller, H., Gulba, D.C. Curr. Biol. (1999) [Pubmed]
  37. Expression of plasminogen activator and inhibitor, urokinase receptor and inhibin subunits in rhesus monkey testes. Zhang, T., Zhou, H.M., Liu, Y.X. Mol. Hum. Reprod. (1997) [Pubmed]
  38. Human retinal pigment epithelial lysis of extracellular matrix: functional urokinase plasminogen activator receptor, collagenase, and elastase. Elner, S.G. Transactions of the American Ophthalmological Society. (2002) [Pubmed]
  39. Regulation of urokinase receptor proteolytic function by the tetraspanin CD82. Bass, R., Werner, F., Odintsova, E., Sugiura, T., Berditchevski, F., Ellis, V. J. Biol. Chem. (2005) [Pubmed]
  40. The urokinase receptor (CD87) facilitates CD11b/CD18-mediated adhesion of human monocytes. Sitrin, R.G., Todd, R.F., Albrecht, E., Gyetko, M.R. J. Clin. Invest. (1996) [Pubmed]
  41. Urokinase-induced signaling in human vascular smooth muscle cells is mediated by PDGFR-beta. Kiyan, J., Kiyan, R., Haller, H., Dumler, I. EMBO J. (2005) [Pubmed]
  42. Expression and colocalization of cytokeratin 1 and urokinase plasminogen activator receptor on endothelial cells. Mahdi, F., Shariat-Madar, Z., Todd, R.F., Figueroa, C.D., Schmaier, A.H. Blood (2001) [Pubmed]
  43. 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. Czekay, R.P., Kuemmel, T.A., Orlando, R.A., Farquhar, M.G. Mol. Biol. Cell (2001) [Pubmed]
  44. Regulation of urokinase receptor expression by p53: novel role in stabilization of uPAR mRNA. Shetty, S., Velusamy, T., Idell, S., Shetty, P., Mazar, A.P., Bhandary, Y.P., Shetty, R.S. Mol. Cell. Biol. (2007) [Pubmed]
  45. Clustering of urokinase receptors (uPAR; CD87) induces proinflammatory signaling in human polymorphonuclear neutrophils. Sitrin, R.G., Pan, P.M., Harper, H.A., Todd, R.F., Harsh, D.M., Blackwood, R.A. J. Immunol. (2000) [Pubmed]
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