ArticleMolecular biology of the cell2001
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.
Article in Molecular biology of the cell, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
74 citing papers in PubMed, 185 citations in OpenAlex.
- Plasminogen Activator Inhibitor-1 is Internalized by Endothelial Cells via A Pinocytosis-Like Mechanism and Evades Degradation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Article
- Review
- Plasminogen activator inhibitor-1 as an oncologic target: biology, therapeutic inhibitors, and clinical translation.Frontiers in oncology · 2026Review
- Targeting uPAR with an antibody-drug conjugate suppresses tumor growth and reshapes the immune landscape in pancreatic cancer models.Science advances · 2025Article
- Novel insights into the multifaceted and tissue-specific roles of the endocytic receptor LRP1.The Journal of biological chemistry · 2024Review
- Packaging of supplemented urokinase into alpha granules of in vitro-grown megakaryocytes for targeted nascent clot lysis.Blood advances · 2024Article
- The uPA/uPAR System Orchestrates the Inflammatory Response, Vascular Homeostasis, and Immune System in Fibrosis Progression.International journal of molecular sciences · 2023Review
- SimulatedPostepy dermatologii i alergologii · 2022Article
- Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer.Journal of translational medicine · 2022Review
- Modulation of Cellular Function by the Urokinase Receptor Signalling: A Mechanistic View.Frontiers in cell and developmental biology · 2022Review
- LRP1B: A Giant Lost in Cancer Translation.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Adipose-PAS interactions in the context of its localised bio-engineering potential (Review).Biomedical reports · 2021Review
- Downregulation of uPAR promotes urokinase translocation into the nucleus and epithelial to mesenchymal transition in neuroblastoma.Journal of cellular physiology · 2020Article
- Molecular imaging of the urokinase plasminogen activator receptor: opportunities beyond cancer.EJNMMI research · 2020Review
- Low Density Receptor-Related Protein 1 Interactions With the Extracellular Matrix: More Than Meets the Eye.Frontiers in cell and developmental biology · 2019Review
- Nanoparticle Binding to Urokinase Receptor on Cancer Cell Surface Triggers Nanoparticle Disintegration and Cargo Release.Theranostics · 2019Article
- Plasminogen activator inhibitor-1 regulates the vascular expression of vitronectin.Journal of thrombosis and haemostasis : JTH · 2017Article
- Identification of LRP-1 as an endocytosis and recycling receptor for β1-integrin in thyroid cancer cells.Oncotarget · 2017Article
- A tripartite complex of suPAR, APOL1 risk variants and αNature medicine · 2017Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Low-density lipoprotein receptor-related protein (LRP) mediates internalization of urokinase:plasminogen activator inhibitor complexes (uPA:PAI-1) and the urokinase receptor (uPAR). Here we investigated whether direct interaction between uPAR, a glycosyl-phosphatidylinositol-anchored protein, and LRP, a transmembrane receptor, is required for clearance of uPA:PAI-1, regeneration of unoccupied uPAR, activation of plasminogen, and the ability of HT1080 cells to invade extracellular matrix. We found that in the absence of uPA:PAI-1, uPAR is randomly distributed along the plasma membrane, whereas uPA:PAI-1 promotes formation of uPAR-LRP complexes and initiates redistribution of occupied uPAR to clathrin-coated pits. uPAR-LRP complexes are endocytosed via clathrin-coated vesicles and traffic together to early endosomes (EE) because they can be coimmunoprecipitated from immunoisolated EE, and internalization is blocked by depletion of intracellular K(+). Direct binding of domain 3 (D3) of uPAR to LRP is required for clearance of uPA-PAI-1-occupied uPAR because internalization is blocked by incubation with recombinant D3. Moreover, uPA-dependent plasmin generation and the ability of HT1080 cells to migrate through Matrigel-coated invasion chambers are also inhibited in the presence of D3. These results demonstrate that GPI-anchored uPAR is endocytosed by piggybacking on LRP and that direct binding of occupied uPAR to LRP is essential for internalization of occupied uPAR, regeneration of unoccupied uPAR, plasmin generation, and invasion and migration through extracellular matrix.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.