Urokinase plasminogen activator surface receptor · UniProt Q03405
PLAUR (uPAR/CD87) is a GPI-anchored receptor that focalizes urokinase-mediated proteolysis at the cell surface and converts that proteolytic context into adhesion and migration signals despite lacking transmembrane and intracellular domains (PMID:12461559). Because it cannot signal autonomously, uPAR transduces information through transmembrane co-receptors: it forms lateral cis complexes with β1 integrins—uPA occupancy converts uPAR into an RGD-dependent ligand for α5β1 that drives MAPK activation and chemotactic migration (PMID:12754207)—and acts in trans, where soluble uPAR engages α4β1, α6β1, α9β1, and αvβ3 on apposing cells in a cation- and RGD-dependent manner (PMID:11053440). On leukocytes it partners physically with the β2 integrin Mac-1/CR3, an association required for integrin-mediated adhesion to endothelium and matrix proteins and reciprocally regulated by uPA occupancy (PMID:9743521, PMID:8874219). Independent of any integrin defect, a direct uPAR–vitronectin interaction is both necessary and sufficient to initiate morphological change, migration, and signaling, as shown by comprehensive alanine-scanning mutagenesis (PMID:17548516). Downstream, uPAR engages RhoB to control cofilin, paxillin, and Akt and to maintain uPAR–integrin association (PMID:22366462), and it triggers tyrosine-kinase-dependent phospholipase C activation with IP3-mediated calcium mobilization (PMID:10570311). The receptor is built from three intertwined LU domains that assemble a high-affinity uPA-binding cavity (PMID:18508598), dimerizes within lipid rafts to favor vitronectin binding and β1-integrin signaling (PMID:14609946, PMID:35351875), and is regulated by D1-cleaving proteases—neutrophil elastase, cathepsin G, and HAT—that release a truncated D2D3 species which itself acts as an FPRL1 chemotactic agonist (PMID:14688365, PMID:17237151, PMID:18830568). uPAR abundance is set transcriptionally by FOXM1, ETV4/PBK, and TCF7L2 and post-transcriptionally by p53-mediated mRNA destabilization, with surface levels further controlled by macropinocytic recycling and LRP1-dependent endocytosis (PMID:17548471, PMID:23136192, PMID:19008962, PMID:21711236). Genetic studies establish physiological roles in platelet–endothelial adhesion, angiogenesis, GABAergic interneuron patterning, and epithelial barrier integrity (PMID:10385508, PMID:21535874, PMID:20381588, PMID:34933179).
Establishing the chromosomal locus and species-specificity of uPA binding anchored PLAUR as a discrete, mappable human gene encoding the urokinase receptor.
Evidence somatic cell hybrid panel, CEPH linkage analysis, and uPA ligand-binding on hybrids
The question of how a proteolytic receptor controls adhesion was answered by showing uPAR physically and functionally couples to the β2 integrin Mac-1/CR3, with uPA occupancy bidirectionally regulating integrin-dependent adhesion.
Evidence anti-uPAR/anti-CR3 mAbs, antisense oligonucleotides, CHO co-transfection of human Mac-1 and uPAR, adhesion and fibrinogen-degradation assays
An in vivo requirement for uPAR in β2-integrin-mediated leukocyte recruitment was established, with domain-1 mapping showing intact uPAR is needed to restore adhesion.
Evidence uPAR-deficient mouse, PI-PLC removal and soluble uPAR reconstitution, mAb ligation, flow cytometry
uPAR aggregation was shown to drive a defined second-messenger cascade—tyrosine-kinase-dependent PLC activation and IP3-mediated calcium release—independent of CR3, establishing intracellular signaling capacity.
Evidence mAb cross-linking, Fluo-3 calcium fluorimetry, IP3 measurement, pharmacological inhibitors in monocytes and U937 cells
Resolving how a GPI-anchored protein signals through integrins, soluble uPAR was shown to act as a direct trans-ligand for multiple β1 and αvβ3 integrins, providing a transmembrane-adapter-free route for cell–cell signaling.
Evidence CHO cell-based binding, anti-integrin and anti-uPAR blocking, integrin function-blocking mutations, ligand competition
The cis-signaling mechanism was defined: uPA binding converts uPAR into an α5β1 ligand requiring the uPA growth-factor domain, coupling proteolytic ligand engagement to MAPK and chemotaxis.
Evidence uPA domain-deletion constructs, anti-uPAR/anti-α5 antibodies, RGD peptides, function-blocking mutations, MAPK inhibition, CHO adhesion/migration assays
Membrane organization was shown to gate function: uPAR dimerizes preferentially in lipid rafts, where vitronectin binding and uPA-induced cleavage are favored, separating dimerization from raft partitioning.
Evidence detergent-resistant membrane fractionation, cholesterol depletion, transmembrane uPAR chimera, cross-linking, flow cytometry
Serpin modulation of vitronectin engagement was clarified—PN-1 enhances while PAI-1 inhibits uPAR–vitronectin adhesion—identifying extracellular regulators of the adhesion ligand axis.
Evidence cell adhesion assays with recombinant PN-1/PAI-1, confocal co-localization, integrin-versus-uPAR pathway discrimination
Regulated proteolysis was defined mechanistically: neutrophil elastase and cathepsin G cleave the D1–D2 linker to generate a D2D3 species and abolish uPA binding, identifying a switch that inactivates the receptor.
Evidence recombinant uPAR substrate cleavage, mass spectrometry of cleavage sites, immunoblot/flow cytometry in U937 and monocytes
A pathogen-exploitation function emerged: streptococcal surface GAPDH binds uPAR domain D1 to mediate bacterial adherence to pharyngeal cells, mapping a host–microbe interface on the receptor.
Evidence ligand-binding assays, LC-MS/MS receptor identification, domain-deletion mapping, SDH mutagenesis, PI-PLC ablation, adherence assays
The vitronectin interaction was elevated to the necessary and sufficient trigger of uPAR signaling, as every morphology-defective mutant in an exhaustive scan lacked vitronectin—not integrin—binding.
Evidence complete alanine scan (255 mutants) in HEK293, morphology/migration assays, membrane-tethered PAI-1 rescue
Transcript-level control was established by showing p53 directly binds the uPAR 3'UTR and destabilizes the mRNA, linking tumor-suppressor status to surface receptor abundance.
Evidence in vitro RNA binding with purified p53, chimeric β-globin–uPAR 3'UTR stability assay, p53 silencing and re-expression
A second D1-shedding protease, airway trypsin-like protease (HAT), was shown to cleave after Arg83/Arg89, producing a D2D3 form unable to bind vitronectin or uPA, extending tissue-specific control of receptor inactivation.
Evidence recombinant substrate cleavage, mass spectrometry, ELISA/flow cytometry, HAT–uPAR co-transfection in epithelial cells
The shed D2D3 fragment was assigned a positive signaling role as an FPRL1 chemotactic agonist, converting receptor cleavage from inactivation into a paracrine motility signal.
Evidence neutrophil activation, immunodepletion of D2D3 from supernatants, FPRL1-transfected HEK293 migration assay, flow cytometry
Receptor turnover was characterized as a constitutive, clathrin- and LRP1-independent macropinocytic recycling route to EEA1+ endosomes, defining how surface uPAR levels are maintained.
Evidence amiloride and PI3K inhibitors, dominant-negative GTPases, cholesterol depletion, electron microscopy, EEA1 co-localization, live imaging
The structural basis of high-affinity uPA capture was defined as a dynamic interdomain assembly of all three LU domains forming a large hydrophobic pocket.
Evidence X-ray crystallography and surface plasmon resonance (reviewed primary structural work)
A neural function was uncovered: uPAR deletion selectively reduces GABAergic interneurons in defined cortical and hippocampal regions with compensatory GABAA subunit shifts and behavioral abnormalities.
Evidence uPAR-/- mice, qRT-PCR of 13 GABAA subunits, in situ hybridization, behavioral testing, regional interneuron counts
uPAR was shown to be required for endothelial adhesion, migration, and angiogenesis, with knockout cells displaying stalled focal adhesions, elevated β1 integrin/FAK/paxillin phosphorylation, and reduced Rac1 activity.
Evidence uPAR-/- endothelial cells, adhesion/migration/tube-formation assays, focal-adhesion immunoblots, Rac1 activity, in vivo Matrigel plug
LRP1 was identified as a route for uPAR endocytosis that down-regulates surface levels and, in some contexts, is required to sustain ERK/PI3K/Rac1 signaling, complementing the macropinocytic pathway.
Evidence review of LRP1 knockdown/inhibition and signaling assays in neurons and Schwann cells
RhoB was placed as a central downstream effector of uPA/uPAR signaling controlling cofilin, paxillin, and Akt and maintaining uPAR–integrin association, linking the receptor to cytoskeletal remodeling in invasion.
Evidence RNAi screen of 12 Rho GTPases, invasion/migration assays, signaling immunoblots, uPAR–integrin co-IP, vitronectin adhesion
Transcriptional drivers of uPAR were defined in cancer: FOXM1 directly activates PLAUR to promote colon cancer growth and metastasis.
Evidence FOXM1 overexpression/knockdown, orthotopic mouse models, expression correlation
Full-length uPAR was shown to be required for both mesenchymal and amoeboid migration, with uPAR–integrin coupling sustaining integrin–actin co-localization and balancing RhoA/Rac1 activity.
Evidence uPAR siRNA, uPAR–integrin blocking peptide, Rho/Rac activity assays, 3D invasion, immunofluorescence
A kinase–transcription-factor axis was defined whereby PBK enhances ETV4 binding to the uPAR promoter to drive metastasis, with ChIP confirming direct ETV4 occupancy.
Evidence ChIP, promoter activity assays, gain/loss-of-function, orthotopic mouse model with uPAR rescue
An epithelial barrier function was uncovered: uPAR loss protects against cytokine-induced barrier breakdown and colitis through enhanced EGF/EGFR signaling.
Evidence CRISPR/siRNA/KO mice, TEER and permeability assays, DSS colitis, small molecule/antibody/peptide inhibitors, EGFR readouts
uPAR was identified as a cell-surface partner of the endostatin-derived E4 fragment required for antifibrotic activation of the urokinase/MMP pathway.
Evidence biotinylated E4 pulldown with MS, uPAR KO cells, in vivo bleomycin fibrosis, MMP activity assays
A high-resolution dimer structure explained how uPAR self-association functions: D1 opens into an expanded ring capturing a neighboring β-hairpin, and the dimer (favored by E49P) increases uPA-ATF binding and drives proliferation via β1 integrin signaling.
Evidence X-ray crystallography at 2.96 Å, E49P mutagenesis, uPA-ATF binding, β1 signaling readouts, immunofluorescence of membrane distribution
Additional transcriptional control and a sensory-neuron signaling role were defined: TCF7L2 activates PLAUR to promote anoikis resistance and metastasis, and uPAR mediates Serpin E1–induced TLR2/OSM signaling driving itch.
Evidence transcriptional/knockdown/overexpression assays and anoikis/metastasis readouts; mouse AD model, sensory neuron transcriptomics, OSM itch assay
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 2002 | uPAR lacks transmembrane and intracellular domains and therefore requires transmembrane co-receptors (notably integrins) for intracellular signaling; it also binds the ECM protein vitronectin as a second ligand critical for signaling. | Review synthesizing multiple experimental studies; mechanistic basis established through prior binding, co-IP, and functional assays documented in primary literature | Nature reviews. Molecular cell biology | High | 12461559 |
| 1998 | uPAR (CD87) forms a functional complex with the beta2 integrin Mac-1 (CD11b/CD18) on leukocytes; this association is required for beta2 integrin-mediated leukocyte adhesion to endothelium and in vivo recruitment to inflamed peritoneum. Removal of uPAR by PI-PLC abolished adhesion, and reassociation with intact (but not domain-1-truncated) soluble uPAR restored it. uPAR ligation with mAb induced adhesion, while ligation with inactivated uPA reduced adhesion. | In vivo uPAR-deficient mouse model; PI-PLC removal and reconstitution of soluble uPAR; monoclonal antibody ligation experiments; flow cytometry | The Journal of experimental medicine | High | 9743521 |
| 1996 | uPAR (CD87) forms a complex with complement receptor 3 (CR3/CD11b/CD18) on human monocytes, and this association facilitates CR3-mediated adhesion to fibrinogen and keyhole limpet hemocyanin. Anti-uPAR mAb and antisense-uPAR oligonucleotides each reduced CR3-dependent adhesion by ~43–50%; uPA occupancy of uPAR negatively regulated this adhesion. | Anti-uPAR and anti-CR3 monoclonal antibodies; antisense oligonucleotides; co-localization by immunofluorescence; adhesion assays | The Journal of clinical investigation | High | 8621779 |
| 1996 | uPAR (CD87) and Mac-1 (CD11b/CD18) form a functional unit on monocytic cells; uPAR-mediated adhesion to vitronectin promotes subsequent Mac-1-mediated fibrinogen/fibrin degradation. Conversely, occupancy of uPAR by urokinase (uPA) or receptor-binding fragments inhibits Mac-1-mediated fibrinogen binding and degradation (up to 91%) and also blocks Factor X binding, demonstrating bidirectional regulation between the two receptors. | TGF-β1/vitamin D3 induction of co-expression; adhesion assays; fibrinogen degradation assays; CHO cell transfection with both human Mac-1 and human uPAR; exogenous uPA inhibition studies | Blood | High | 8874219 |
| 2000 | Soluble uPAR (suPAR) acts as a direct integrin ligand (trans-interaction) for integrins α4β1, α5β1 (implied), α6β1, α9β1, and αvβ3, binding in a cation-dependent, RGD-dependent manner. GPI-anchored uPAR on one cell surface can also bind integrins on apposing cells (trans-interaction), suggesting a mechanism for cell–cell interaction and integrin-mediated signaling without a transmembrane adapter. | Cell-based binding assays on CHO cells; blocking with anti-integrin and anti-uPAR antibodies; integrin function-blocking mutations; competition with soluble integrin ligands | The Journal of biological chemistry | High | 11053440 |
| 2003 | uPA binding to uPAR causes uPAR to act as a ligand for integrin α5β1 in cis, inducing RGD-dependent cell adhesion, MAPK activation, and chemotactic migration. The growth factor domain (GFD) of uPA is required; neither kringle nor serine protease domains alone support adhesion. Signal transduction proceeds through α5β1 after uPA→uPAR→α5β1 complex assembly. | Anti-uPAR and anti-α5 antibodies; RGD peptides; α5β1 function-blocking mutations; uPA domain deletion constructs; MAPK inhibition; CHO cell adhesion and migration assays | The Journal of biological chemistry | High | 12754207 |
| 2003 | Cell-surface uPAR dimerizes, and dimeric uPAR partitions preferentially into detergent-resistant lipid rafts. Vitronectin (Vn) binding occurs preferentially to raft-associated dimeric uPAR and is completely blocked by cholesterol depletion. uPA-induced uPAR cleavage is strongly accelerated in lipid rafts. Dimerization itself does not require raft partitioning (a transmembrane uPAR chimera outside rafts still dimerizes efficiently). | Detergent-resistant membrane fractionation; cholesterol depletion; transmembrane uPAR chimera; cross-linking; flow cytometry; ligand-binding assays | The EMBO journal | High | 14609946 |
| 2004 | Neutrophil elastase and cathepsin G cleave uPAR (CD87) within the D1–D2 linker sequence, generating truncated D2D3 membrane species and releasing them from monocytic cell surfaces. Cathepsin G additionally cleaves the C-terminus of D3. Combined action of both enzymes cooperatively generates a truncated D2D3 form similar to that found in pathological body fluids. These cleavages drastically reduce the capacity of cells to bind urokinase. | Immunoblotting; flow cytometry; mass spectrometry of synthetic peptide fragments; recombinant uPAR substrate; U937 cells and isolated blood monocytes | Journal of immunology | High | 14688365 |
| 2007 | A direct uPAR–vitronectin interaction is both necessary and sufficient to initiate downstream changes in cell morphology, migration, and signal transduction. A complete alanine scan of uPAR (255 mutants) showed that all 34 morphology-defective mutants specifically lacked vitronectin binding; no integrin-binding defect was necessary. A membrane-tethered PAI-1 (which has the same vitronectin binding site as uPAR) replicated uPAR-induced morphological changes. | Complete functional alanine scanning mutagenesis (255 mutants) in HEK293 cells; cell morphology/migration assays; membrane-tethered PAI-1 rescue experiment | The Journal of cell biology | High | 17548516 |
| 1999 | uPAR aggregation (by mAb cross-linking) triggers phospholipase C activation via a tyrosine kinase-dependent mechanism, generating Ins(1,4,5)P3 and mobilizing intracellular calcium from IP3-sensitive stores. Cross-linking CR3 did not replicate this effect, and anti-CR3 antibodies did not block uPAR-triggered Ca2+ mobilization, indicating independence from CR3. | Fluo-3 fluorimetry for [Ca2+]i; mAb cross-linking of uPAR; IP3 measurement; pharmacological inhibitors (thapsigargin, herbimycin A, U73122); primary human monocytes and U937 cells | Journal of immunology | High | 10570311 |
| 1995 | uPAR (CD87) is required for neutrophil (PMN) chemotaxis in vitro by a mechanism independent of uPA enzymatic activity, potentially through its ability to associate with CR3. Specific saccharides that disrupt CD87/CR3 coupling (NADG, D-mannose, mannoside) also inhibited PMN chemotaxis. | Anti-CD87 mAb pre-treatment of PMNs; anti-uPA mAb and exogenous uPA controls; saccharide-mediated CR3/uPAR uncoupling; chemotaxis assay | Journal of leukocyte biology | Medium | 7595054 |
| 2007 | p53 protein binds directly to a 37-nucleotide sequence in the 3' UTR of uPAR mRNA, destabilizes uPAR mRNA, and thereby suppresses uPAR expression. Loss of p53 stabilizes uPAR mRNA and increases cell-surface uPAR levels; inserting the p53-binding sequence into beta-globin mRNA confers p53-dependent destabilization to the chimeric transcript. | RNA binding assay with purified p53; RNA silencing of p53; chimeric beta-globin–uPAR 3'UTR mRNA stability assay; p53 expression in p53-null cells | Molecular and cellular biology | High | 17548471 |
| 2007 | The human airway trypsin-like protease (HAT) cleaves uPAR in the D1–D2 linker sequence after Arg83 and Arg89, generating a truncated D2D3 form that cannot bind vitronectin or urokinase. Membrane co-expression of HAT and uPAR causes constitutive and extensive shedding of the D1 domain. | Immunoblotting; flow cytometry; ELISA; mass spectrometry (site identification); co-transfection in epithelial cells; recombinant uPAR substrate | American journal of physiology. Lung cellular and molecular physiology | High | 17237151 |
| 2005 | Streptococcal surface GAPDH (SDH/GAS) binds uPAR/CD87 specifically through the N-terminal domain D1 of uPAR, and this interaction mediates bacterial adherence to human pharyngeal cells. SDH binding maps to the C-terminal alpha-helix and flanking S-loop regions of SDH. PI-PLC removal of uPAR from pharyngeal cells decreased GAS adherence. | Ligand-binding assays; LC-MS/MS identification of the ~55 kDa SDH receptor as uPAR; domain-deletion mapping; site-directed mutagenesis of SDH; PI-PLC removal of uPAR; bacterial adherence assays | Journal of molecular biology | High | 15922359 |
| 2008 | uPAR undergoes constitutive (ligand-independent) endocytosis and recycling through a clathrin- and LRP-1-independent macropinocytic pathway. This pathway is amiloride-sensitive, does not require lipid raft partitioning, and is independent of RhoA, Rac1, Cdc42, and PI3K. Constitutively endocytosed uPAR reaches EEA1-positive early/recycling endosomes but not lysosomes. | Pharmacological inhibitors (amiloride, PI3K inhibitors); dominant-negative small GTPases; cholesterol depletion; electron microscopy; EEA1 co-localization; live imaging | PloS one | Medium | 19008962 |
| 2011 | LRP1 facilitates the endocytosis of uPAR, thereby down-regulating cell-surface uPAR levels and modulating uPAR-initiated signaling (ERK, PI3K, Rac1). Under some conditions uPAR endocytosis via LRP1 is required for sustained uPAR-initiated cell-signaling. | Review of primary experimental evidence including LRP1 knockdown/inhibition studies and cell-signaling assays in neurons, neuron-like cells, and Schwann cells (primary literature basis) | Current pharmaceutical design | Medium | 21711236 |
| 2008 | Activated human neutrophils rapidly shed uPAR predominantly as a truncated D2D3 form (lacking D1 and the GPI anchor). This D2D3 form acts as a chemotactic agonist via FPRL1 (formyl peptide receptor-like 1): immunodepletion of D2D3 from activated neutrophil supernatants significantly reduced migration of FPRL1-transfected HEK293 cells. GPI-specific phospholipase D is not involved in uPAR shedding from neutrophils. | Ionomycin/TNF-α/fMLP/IL-8 activation; immunodepletion of D2D3 from supernatants; FPRL1-transfected HEK293 migration assay; flow cytometry | Molecular and cellular biochemistry | Medium | 18830568 |
| 2008 | The central binding cavity of uPAR for uPA is assembled by a dynamic interdomain association of all three LU domains; the high-affinity interaction (KD < 1 nM) relies on an unusually large and hydrophobic binding pocket. This structural information was established by X-ray crystallography and surface plasmon resonance. | X-ray crystallography; surface plasmon resonance (as reviewed citing primary structural studies) | Frontiers in bioscience | High | 18508598 |
| 2012 | RhoB is a key downstream regulator of uPAR signaling: uPA/uPAR rapidly activates RhoB and increases RhoB expression; RhoB depletion by RNAi reduces uPA-induced migration and invasion of prostate carcinoma cells, inhibits uPAR signaling to cofilin, paxillin, and Akt, and reduces integrin levels and uPAR–integrin association. Cell adhesion to vitronectin (a uPAR ligand) is also impaired by RhoB depletion. | RNAi screen of 12 Rho GTPases; invasion/migration assays; immunoblotting for cofilin, paxillin, Akt; co-immunoprecipitation of uPAR and integrins; vitronectin adhesion assays | Journal of cell science | Medium | 22366462 |
| 2014 | Full-length uPAR is required for both mesenchymal and amoeboid migration modes in cancer cells. uPAR co-localizes with β1/β3 integrins and the actin cytoskeleton; a peptide inhibiting uPAR–integrin interaction disrupts integrin–actin co-localization and abolishes amoeboid invasion while also reducing mesenchymal invasion. uPAR silencing deregulates RhoA and Rac1 GTPase activities during the amoeboid switch. | uPAR siRNA silencing; uPAR–integrin blocking peptide; Rho/Rac GTPase activity assays; 3D matrix invasion assays; immunofluorescence co-localization | Oncotarget | Medium | 24681666 |
| 2012 | FOXM1 transcription factor directly activates PLAUR (uPAR) gene expression, promoting colon cancer growth and metastasis. FOXM1 overexpression significantly upregulates uPAR expression and increases invasion/metastasis in orthotopic mouse models; FOXM1 knockdown reduces uPAR expression and metastasis. | Gene transfer overexpression and siRNA knockdown of FOXM1; orthotopic mouse models; correlation of FOXM1 and PLAUR expression | Clinical cancer research | Medium | 23136192 |
| 2019 | PBK kinase enhances uPAR (PLAUR) expression by activating its promoter via ETV4. ChIP showed ETV4 directly binds the core region of the uPAR promoter, and PBK enhances ETV4 binding to this promoter. In vivo, PBK knockdown inhibited lung metastasis of HCC cells, an effect rescued by uPAR overexpression. | Chromatin immunoprecipitation (ChIP); promoter activity assay; gain/loss-of-function; orthotopic mouse model; ETV4–uPAR promoter interaction | Cancer letters | Medium | 30914208 |
| 2022 | TCF7L2 transcriptionally activates PLAUR (uPAR) expression; TCF7L2 promotes anoikis resistance and metastasis of gastric cancer cells through upregulation of PLAUR. | Transcriptional activation assays; siRNA knockdown; overexpression studies; anoikis and metastasis assays | International journal of biological sciences | Medium | 35864968 |
| 2022 | Crystal structure of human uPAR dimer at 2.96 Å resolution reveals that dimerization causes D1 to open into a large expanded ring that captures a β-hairpin loop of a neighboring uPAR, forming an extended β-sheet and an elongated, highly intertwined dimer. Mutation E49P promotes dimer formation; the dimer shows increased binding to the amino-terminal fragment of uPA, redistributes to the basal membrane, promotes cell proliferation, and alters cell morphology via β1 integrin signaling. | X-ray crystallography (2.96 Å); site-directed mutagenesis (E49P); cell-based functional assays; β1 integrin signaling readouts; uPA-ATF binding assay; immunofluorescence for membrane distribution | Nature communications | High | 35351875 |
| 2003 | Protease nexin-1 (PN-1) unexpectedly increases the association between vitronectin and uPAR in the presence of enzymatically active uPA, thereby stimulating uPAR-dependent cell adhesion to immobilized vitronectin. In contrast, PAI-1 inhibits uPAR–vitronectin interaction. On adhesion to vitronectin, uPAR and PN-1 co-accumulate at the cell–matrix interface. | Cell adhesion assays; confocal microscopy; PN-1 and PAI-1 protein additions; integrin versus uPAR adhesion pathway discrimination | Journal of cell science | Medium | 14679304 |
| 1999 | uPAR (CD87) functions as a platelet receptor; uPAR-deficient platelets survive longer in wild-type recipients, and TNF-induced platelet consumption, pulmonary localization, and platelet activation are absent in uPAR-/- mice. Platelet uPAR (not endothelial/leukocyte uPAR) is critical for TNF-induced platelet–endothelial adhesion. | uPAR-/- mouse model; 51Cr platelet survival assay; intratracheal TNF injection; FACS; electron microscopy; cross-transfer experiments | Circulation | High | 10385508 |
| 2010 | Genetic disruption of PLAUR (uPAR null mice) causes a regionally selective reduction in GABAergic interneurons in frontal and parietal neocortex and hippocampal CA1 and dentate gyrus, with compensatory changes in GABAA receptor subunit composition (α2 up, α3 down, β2/β3/γ2 subunit changes) specifically in regions with interneuron loss, and associated behavioral phenotypes (increased seizure sensitivity, anxiety, atypical social behavior). | uPAR-/- mice; quantitative RT-PCR for 13 GABAA subunits; semi-quantitative in situ hybridization; behavioral testing; regional interneuron counting | Neuroscience | Medium | 20381588 |
| 2021 | Genetic inhibition of uPAR (CRISPR, siRNA, uPAR-KO mice) or pharmacological blockade of uPA–uPAR interaction protects intestinal epithelial barrier integrity against cytokine-induced breakdown. uPAR deficiency in epithelial cells leads to enhanced EGF/EGFR signaling. uPAR-deficient mice display improved barrier function and attenuated DSS-induced colitis. | CRISPR, siRNA, KO mice; TEER and FITC-dextran permeability; tight junction assessment; DSS colitis model; small molecule, neutralizing antibody and peptide inhibitors; EGFR signaling readouts | EBioMedicine | High | 34933179 |
| 2022 | PLAUR (uPAR) in sensory neurons mediates Serpin E1 (PAI-1)-induced signaling through TLR2 co-activation and downstream OSM production, promoting itch-associated gene transcription. PLAUR resides in TLR2+ sensory neurons; Serpin E1 stimulus upregulates TLR2 and its co-signaling proteins; OSM induces acute itch in mice. | Mouse AD model (MC903); sensory neuron isolation; transcriptomic profiling; in vivo Serpin E1 inhibitor treatment; OSM itch assay in mice; human AD/psoriasis skin specimens | FASEB journal | Medium | 35596683 |
| 1992 | The PLAUR gene (encoding uPAR) maps to human chromosome 19q13.1–q13.2. A ligand-binding study on cell hybrids confirmed species-specificity of uPAR and validated the chromosomal assignment. | Human/rodent somatic cell hybrid panel; multipoint linkage analysis of CEPH families; uPA ligand-binding assay on cell hybrids | American journal of human genetics | High | 1311495 |
| 2021 | E4 (C-terminal endostatin domain) binds uPAR (and enolase-1) at the cell surface; this interaction is required for E4's antifibrotic effects. E4 activates the urokinase pathway, increases the uPA/PAI-1 ratio, and elevates MMP-1 and MMP-3 expression and activity in a uPAR-dependent manner. | Biotinylated E4 pulldown with MS identification of binding partners; uPAR KO cells; in vivo bleomycin fibrosis model; MMP activity assays | JCI insight | Medium | 34935642 |
| 2011 | uPAR deficiency (uPAR-/-) in murine endothelial cells impairs adhesion, migration, proliferation, and capillary tube formation. On vitronectin, uPAR-/- cells adopt a 'fried egg' morphology with circular actin and no lamellipodia, with upregulated β1 integrin, FAK(P-Tyr925), and paxillin (P-Tyr118) indicating increased but stalled focal adhesions, and decreased Rac1 activation. In vivo, uPAR-/- mice show lack of mature vessel formation in VEGF-enriched Matrigel implants. | uPAR-/- murine endothelial cells; adhesion/migration/proliferation/tube formation assays; immunoblotting for focal adhesion proteins; Rac1 activity assay; in vivo Matrigel plug assay | Vascular cell | Medium | 21535874 |
| Year | Title | Journal | Citations | PMID |
|---|---|---|---|---|
| 2002 | uPAR: a versatile signalling orchestrator. | Nature reviews. Molecular cell biology | 1054 | 12461559 |
| 2010 | Regulation of cell signalling by uPAR. | Nature reviews. Molecular cell biology | 782 | 20027185 |
| 2007 | Evolving role of uPA/uPAR system in human cancers. | Cancer treatment reviews | 342 | 18162327 |
| 1998 | Urokinase receptor (CD87) regulates leukocyte recruitment via beta 2 integrins in vivo. | The Journal of experimental medicine | 239 | 9743521 |
| 2007 | uPAR-uPA-PAI-1 interactions and signaling: a vascular biologist's view. | Thrombosis and haemostasis | 206 | 17334498 |
| 2007 | uPAR-induced cell adhesion and migration: vitronectin provides the key. | The Journal of cell biology | 198 | 17548516 |
| 1996 | The urokinase receptor (CD87) facilitates CD11b/CD18-mediated adhesion of human monocytes. | The Journal of clinical investigation | 180 | 8621779 |
| 1996 | Mac-1 (CD11b/CD18) and the urokinase receptor (CD87) form a functional unit on monocytic cells. | Blood | 165 | 8874219 |
| 2016 | Organization, evolution and functions of the human and mouse Ly6/uPAR family genes. | Human genomics | 164 | 27098205 |
| 2000 | Urokinase-type plasminogen activator receptor (CD87) is a ligand for integrins and mediates cell-cell interaction. | The Journal of biological chemistry | 153 | 11053440 |
| 2004 | Clinical significance of urokinase-type plasminogen activator receptor (uPAR) expression in cancer. | Medicinal research reviews | 134 | 14595671 |
| 2006 | uPAR and HER-2 gene status in individual breast cancer cells from blood and tissues. | Proceedings of the National Academy of Sciences of the United States of America | 128 | 17079488 |
| 2003 | Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions. | The EMBO journal | 120 | 14609946 |
| 1998 | Role of urokinase (uPA) and its receptor (uPAR) in invasion and metastasis of hormone-dependent malignancies. | International journal of oncology | 117 | 9499455 |
| 2015 | First-in-human uPAR PET: Imaging of Cancer Aggressiveness. | Theranostics | 102 | 26516369 |
| 2012 | The critical role of dysregulated FOXM1-PLAUR signaling in human colon cancer progression and metastasis. | Clinical cancer research : an official journal of the American Association for Cancer Research | 101 | 23136192 |
| 2005 | Group A streptococcal surface GAPDH, SDH, recognizes uPAR/CD87 as its receptor on the human pharyngeal cell and mediates bacterial adherence to host cells. | Journal of molecular biology | 95 | 15922359 |
| 2012 | VEGF-initiated angiogenesis and the uPA/uPAR system. | Cell adhesion & migration | 89 | 23076133 |
| 2022 | Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer. | Journal of translational medicine | 86 | 35303878 |
| 1995 | Function of the urokinase receptor (CD87) in neutrophil chemotaxis. | Journal of leukocyte biology | 85 | 7595054 |
| 2007 | Targeting uPA/uPAR in prostate cancer. | Cancer treatment reviews | 83 | 17658220 |
| 2022 | TCF7L2 promotes anoikis resistance and metastasis of gastric cancer by transcriptionally activating PLAUR. | International journal of biological sciences | 82 | 35864968 |
| 2004 | The urokinase receptor (uPAR) and the uPAR-associated protein (uPARAP/Endo180): membrane proteins engaged in matrix turnover during tissue remodeling. | Biological chemistry | 80 | 15101555 |
| 2009 | Multiple activities of a multifaceted receptor: roles of cleaved and soluble uPAR. | Frontiers in bioscience (Landmark edition) | 79 | 19273214 |
| 2019 | PBK overexpression promotes metastasis of hepatocellular carcinoma via activating ETV4-uPAR signaling pathway. | Cancer letters | 78 | 30914208 |
| 2001 | The urokinase plasminogen activator receptor (uPAR) as a target for the diagnosis and therapy of cancer. | Anti-cancer drugs | 76 | 11395568 |
| 2011 | uPAR as anti-cancer target: evaluation of biomarker potential, histological localization, and antibody-based therapy. | Current drug targets | 73 | 21707477 |
| 2020 | COVID-19 and pneumonia: a role for the uPA/uPAR system. | Drug discovery today | 68 | 32562843 |
| 2017 | Urokinase-type plasminogen activator receptor (uPAR) expression enhances invasion and metastasis in RAS mutated tumors. | Scientific reports | 68 | 28839232 |
| 2009 | PLAUR polymorphisms are associated with asthma, PLAUR levels, and lung function decline. | The Journal of allergy and clinical immunology | 68 | 19443020 |
| 2003 | Critical role of integrin alpha 5 beta 1 in urokinase (uPA)/urokinase receptor (uPAR, CD87) signaling. | The Journal of biological chemistry | 66 | 12754207 |
| 1998 | The urokinase-type-plasminogen-activator receptor (CD87) is a pleiotropic molecule. | European journal of biochemistry | 66 | 9523687 |
| 2004 | Proteolytic regulation of the urokinase receptor/CD87 on monocytic cells by neutrophil elastase and cathepsin G. | Journal of immunology (Baltimore, Md. : 1950) | 64 | 14688365 |
| 2003 | Urokinase-type plasminogen activator (uPA) and its receptor (uPAR): development of antagonists of uPA/uPAR interaction and their effects in vitro and in vivo. | Current pharmaceutical design | 64 | 12871066 |
| 2008 | Structure and ligand interactions of the urokinase receptor (uPAR). | Frontiers in bioscience : a journal and virtual library | 63 | 18508598 |
| 2008 | Activated human neutrophils rapidly release the chemotactically active D2D3 form of the urokinase-type plasminogen activator receptor (uPAR/CD87). | Molecular and cellular biochemistry | 62 | 18830568 |
| 2011 | Clinical applications of the urokinase receptor (uPAR) for cancer patients. | Current pharmaceutical design | 61 | 21711239 |
| 2011 | Rational targeting of the urokinase receptor (uPAR): development of antagonists and non-invasive imaging probes. | Current drug targets | 60 | 21707479 |
| 2012 | Subpopulation of small-cell lung cancer cells expressing CD133 and CD87 show resistance to chemotherapy. | Cancer science | 56 | 23066953 |
| 2004 | CD87 (urokinase-type plasminogen activator receptor), function and pathology in hematological disorders: a review. | Leukemia | 56 | 14671631 |
| 2008 | Clathrin and LRP-1-independent constitutive endocytosis and recycling of uPAR. | PloS one | 55 | 19008962 |
| 1994 | Cytokine-specific regulation of urokinase receptor (CD87) expression by U937 mononuclear phagocytes. | Blood | 55 | 8049441 |
| 2021 | Targeting uPA-uPAR interaction to improve intestinal epithelial barrier integrity in inflammatory bowel disease. | EBioMedicine | 50 | 34933179 |
| 2017 | Three-Finger Proteins from the Ly6/uPAR Family: Functional Diversity within One Structural Motif. | Biochemistry. Biokhimiia | 50 | 29523067 |
| 2018 | uPA/uPAR signaling in rheumatoid arthritis: Shedding light on its mechanism of action. | Pharmacological research | 48 | 29859810 |
| 2007 | Tumoral and macrophage uPAR and MMP-9 contribute to the invasiveness of B16 murine melanoma cells. | Clinical & experimental metastasis | 47 | 18071911 |
| 1992 | Assignment of the urokinase-type plasminogen activator receptor gene (PLAUR) to chromosome 19q13.1-q13.2. | American journal of human genetics | 45 | 1311495 |
| 2015 | uPAR-targeted multimodal tracer for pre- and intraoperative imaging in cancer surgery. | Oncotarget | 44 | 25895028 |
| 2007 | Urinary-type plasminogen activator (uPA) and its receptor (uPAR) in squamous cell carcinoma of the oral cavity. | The Biochemical journal | 42 | 17880283 |
| 2000 | Lesion associated expression of urokinase-type plasminogen activator receptor (uPAR, CD87) in human cerebral malaria. | Journal of neuroimmunology | 42 | 11063844 |
| 2001 | Borrelia burgdorferi and other bacterial products induce expression and release of the urokinase receptor (CD87). | Journal of immunology (Baltimore, Md. : 1950) | 41 | 11123326 |
| 1999 | Characterization of cell-associated plasminogen activation catalyzed by urokinase-type plasminogen activator, but independent of urokinase receptor (uPAR, CD87). | Blood | 41 | 10339491 |
| 2011 | Regulation of the urokinase receptor (uPAR) by LDL receptor-related protein-1 (LRP1). | Current pharmaceutical design | 39 | 21711236 |
| 2010 | The autism risk genes MET and PLAUR differentially impact cortical development. | Autism research : official journal of the International Society for Autism Research | 39 | 21328570 |
| 2021 | The Urokinase Receptor (uPAR) as a "Trojan Horse" in Targeted Cancer Therapy: Challenges and Opportunities. | Cancers | 38 | 34771541 |
| 2014 | The receptor for urokinase-plasminogen activator (uPAR) controls plasticity of cancer cell movement in mesenchymal and amoeboid migration style. | Oncotarget | 38 | 24681666 |
| 2007 | The human airway trypsin-like protease modulates the urokinase receptor (uPAR, CD87) structure and functions. | American journal of physiology. Lung cellular and molecular physiology | 38 | 17237151 |
| 2012 | MMP-9 and uPAR regulated glioma cell migration. | Cell adhesion & migration | 37 | 23076139 |
| 2018 | PLAUR Confers Resistance to Gefitinib Through EGFR/P-AKT/Survivin Signaling Pathway. | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 36 | 29961070 |
| 1995 | Urokinase-type plasminogen activator (uPA) and its receptor (CD87): a new target in tumor invasion and metastasis. | Journal of obstetrics and gynaecology (Tokyo, Japan) | 36 | 8556577 |
| 2012 | The urokinase receptor (CD87) represents a central mediator of growth factor-induced endothelial cell migration. | Thrombosis and haemostasis | 35 | 22782499 |
| 1996 | Mechanisms of pertussis toxin-induced myelomonocytic cell adhesion: role of Mac-1(CD11b/CD18) and urokinase receptor (CD87). | Immunology | 35 | 8707356 |
| 2024 | Urokinase-Type Plasminogen Activator Receptor (uPAR) in Inflammation and Disease: A Unique Inflammatory Pathway Activator. | Biomedicines | 34 | 38927374 |
| 2021 | uPAR: An Essential Factor for Tumor Development. | Journal of Cancer | 34 | 34729105 |
| 2001 | High level synthesis of recombinant soluble urokinase receptor (CD87) by ovarian cancer cells reduces intraperitoneal tumor growth and spread in nude mice. | Biological chemistry | 34 | 11517932 |
| 1998 | Urokinase plasminogen activator receptor (uPAR; CD87) expression on monocytic cells and T cells is modulated by HIV-1 infection. | Immunobiology | 34 | 9717675 |
| 2011 | Structural basis for therapeutic intervention of uPA/uPAR system. | Current drug targets | 33 | 21707478 |
| 2007 | Regulation of urokinase receptor expression by p53: novel role in stabilization of uPAR mRNA. | Molecular and cellular biology | 32 | 17548471 |
| 1999 | Urokinase receptor (uPAR, CD87) is a platelet receptor important for kinetics and TNF-induced endothelial adhesion in mice. | Circulation | 32 | 10385508 |
| 1999 | Urokinase receptor (CD87) aggregation triggers phosphoinositide hydrolysis and intracellular calcium mobilization in mononuclear phagocytes. | Journal of immunology (Baltimore, Md. : 1950) | 31 | 10570311 |
| 2017 | Preclinical uPAR-targeted multimodal imaging of locoregional oral cancer. | Oral oncology | 30 | 28249642 |
| 2008 | Endothelial cells and normal breast epithelial cells enhance invasion of breast carcinoma cells by CXCR-4-dependent up-regulation of urokinase-type plasminogen activator receptor (uPAR, CD87) expression. | The Journal of pathology | 30 | 18189329 |
| 1999 | UVB increases urokinase-type plasminogen activator receptor (uPAR) expression. | The Journal of investigative dermatology | 30 | 10417621 |
| 2013 | Urokinase plasminogen activator receptor (uPAR) targeted nuclear imaging and radionuclide therapy. | Theranostics | 29 | 23843898 |
| 2003 | The diphtheria toxin/urokinase fusion protein (DTAT) is selectively toxic to CD87 expressing leukemic cells. | Leukemia research | 29 | 12479856 |
| 1997 | The urokinase-receptor (CD87) is expressed in cells of the megakaryoblastic lineage. | Thrombosis and haemostasis | 28 | 9066008 |
| 2021 | Development of inhibitors for uPAR: blocking the interaction of uPAR with its partners. | Drug discovery today | 27 | 33486111 |
| 2014 | uPAR and cathepsin B-mediated compartmentalization of JNK regulates the migration of glioma-initiating cells. | Stem cell research | 27 | 24699410 |
| 2009 | PLAUR polymorphisms and lung function in UK smokers. | BMC medical genetics | 27 | 19878584 |
| 2012 | RhoB regulates uPAR signalling. | Journal of cell science | 26 | 22366462 |
| 2005 | Expression of urokinase-type plasminogen activator receptor (uPAR) in primary central nervous system neoplasms. | Applied immunohistochemistry & molecular morphology : AIMM | 26 | 15894933 |
| 2019 | CD49b, CD87, and CD95 Are Markers for Activated Cancer-Associated Fibroblasts Whereas CD39 Marks Quiescent Normal Fibroblasts in Murine Tumor Models. | Frontiers in oncology | 25 | 31428583 |
| 2015 | HER2 and uPAR cooperativity contribute to metastatic phenotype of HER2-positive breast cancer. | Oncoscience | 25 | 25897424 |
| 2012 | Characterization and function of human Ly-6/uPAR molecules. | BMB reports | 25 | 23186997 |
| 2021 | Targeting the Urokinase-Type Plasminogen Activator Receptor (uPAR) in Human Diseases With a View to Non-invasive Imaging and Therapeutic Intervention. | Frontiers in cell and developmental biology | 24 | 34490277 |
| 2020 | uPAR antibody (huATN-658) and Zometa reduce breast cancer growth and skeletal lesions. | Bone research | 24 | 32337090 |
| 2019 | Relating GPI-Anchored Ly6 Proteins uPAR and CD59 to Viral Infection. | Viruses | 24 | 31739586 |
| 2010 | Genetic disruption of the autism spectrum disorder risk gene PLAUR induces GABAA receptor subunit changes. | Neuroscience | 24 | 20381588 |
| 2003 | Reciprocal regulation of urokinase receptor (CD87)-mediated cell adhesion by plasminogen activator inhibitor-1 and protease nexin-1. | Journal of cell science | 24 | 14679304 |
| 2020 | Curcumol may reverse early and advanced liver fibrogenesis through downregulating the uPA/uPAR pathway. | Phytotherapy research : PTR | 23 | 31989700 |
| 2013 | Tumor-associated soluble uPAR-directed endothelial cell motility and tumor angiogenesis. | Oncogenesis | 22 | 23797476 |
| 2009 | ECRG2 regulates ECM degradation and uPAR/FPRL1 pathway contributing cell invasion/migration. | Cancer letters | 22 | 19796867 |
| 2021 | HIF-Dependent NFATC1 Activation Upregulates ITGA5 and PLAUR in Intestinal Epithelium in Inflammatory Bowel Disease. | Frontiers in genetics | 21 | 34858489 |
| 2025 | PLAUR+ Neutrophils Drive Anti-PD-1 Therapy Resistance in Patients with Hepatocellular Carcinoma by Shaping an Immunosuppressive Microenvironment. | Advanced science (Weinheim, Baden-Wurttemberg, Germany) | 20 | 40673864 |
| 2021 | E4 engages uPAR and enolase-1 and activates urokinase to exert antifibrotic effects. | JCI insight | 20 | 34935642 |
| 2019 | The uPAR System as a Potential Therapeutic Target in the Diseased Eye. | Cells | 20 | 31426601 |
| 2011 | A deficiency of uPAR alters endothelial angiogenic function and cell morphology. | Vascular cell | 19 | 21535874 |
| 2010 | Association of putative functional variants in the PLAU gene and the PLAUR gene with myocardial infarction. | Clinical science (London, England : 1979) | 19 | 20518747 |
| 2022 | Crystal structure and cellular functions of uPAR dimer. | Nature communications | 18 | 35351875 |
| 2022 | The PLAUR signaling promotes chronic pruritus. | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 18 | 35596683 |
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