ArticleProceedings of the National Academy of Sciences of the United States of America2002
The fibrinolytic receptor for urokinase activates the G protein-coupled chemotactic receptor FPRL1/LXA4R.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers.
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Who cites it
148 citing papers in PubMed, 354 citations in OpenAlex.
- uPAR/suPAR Signaling and Organ Crosstalk in Cardiovascular-Kidney-Metabolic Syndrome.Circulation research · 2026Review
- Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) as a Biomarker of Neurodysfunction.Neuromolecular medicine · 2026Review
- TheFrontiers in immunology · 2025Review
- Identification of Pathogenic Pathways for Recurrence of Focal Segmental Glomerulosclerosis after Kidney Transplantation.Diagnostics (Basel, Switzerland) · 2024Article
- Urokinase-Type Plasminogen Activator Receptor (uPAR) in Inflammation and Disease: A Unique Inflammatory Pathway Activator.Biomedicines · 2024Review
- Dysregulated fibrinolysis and plasmin activation promote the pathogenesis of osteoarthritis.JCI insight · 2024Article
- Article
- Urokinase-Type Plasminogen Activator Receptor Regulates Prosurvival and Angiogenic Properties of Cardiac Mesenchymal Stromal Cells.International journal of molecular sciences · 2023Article
- Redrawing Urokinase Receptor (uPAR) Signaling with Cancer Driver Genes for Exploring Possible Anti-Cancer Targets and Drugs.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity.Clinical and translational allergy · 2023Article
- Macrophages and Urokinase Plasminogen Activator Receptor System in Multiple Myeloma: Case Series and Literature Review.International journal of molecular sciences · 2023Review
- Acquired hyperfibrinolysis as the presenting sign of metastatic breast cancer: A case report.Oncology letters · 2023Article
- bFGF stimulated plasminogen activation factors, but inhibited alkaline phosphatase and SPARC in stem cells from apical Papilla: Involvement of MEK/ERK, TAK1 and p38 signaling.Journal of advanced research · 2022Article
- Molecular Pharmacology of Inflammation Resolution in Atherosclerosis.International journal of molecular sciences · 2022Review
- In Vitro and In Vivo Effects of the Urokinase Plasminogen Activator Inhibitor WX-340 on Anaplastic Thyroid Cancer Cell Lines.International journal of molecular sciences · 2022Article
- Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer.Journal of translational medicine · 2022Review
- Review
- Modulation of Cellular Function by the Urokinase Receptor Signalling: A Mechanistic View.Frontiers in cell and developmental biology · 2022Review
- suPAR to Risk-Stratify Patients With Malaria.Frontiers in immunology · 2022Review
- The Urokinase Receptor (uPAR) as a "Trojan Horse" in Targeted Cancer Therapy: Challenges and Opportunities.Cancers · 2021Review
88 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The function of urokinase and its receptor is essential for cell migration in pathological conditions, as shown by the analysis of knockout mice phenotypes. How a protease of a fibrinolytic pathway can induce migration is not understood and no link between this protease and migration-promoting G protein-coupled receptors has been described. We now show that FPRL1/LXA4R, a G protein-coupled receptor for a number of polypeptides and for the endogenous lipoxin A4 (LXA4), is the link between urokinase-type plasminogen activator (uPA) and migration as it directly interacts with an activated, soluble, cleaved form of uPA receptor (uPAR) (D2D3(88-274)) to induce chemotaxis. In this article we show that (i) both uPAR and FPRL1/LXA4R are necessary for the chemotactic activity of uPA whereas FPRL1/LXA4R is sufficient to mediate D2D3(88-274)-induced cell migration. (ii) Inhibition or desensitization of FPRL1/LXA4R by antibodies or specific ligands specifically prevents chemotaxis induced by D2D3(88-274) in THP-1 cells and human peripheral blood monocytes. (iii) Desensitization of FPRL1/LXA4R prevents the activation of tyrosine kinase Hck induced by D2D3(88-274). (iv) D2D3(88-274) directly binds to FPRL1/LXA4R and is competed by two specific FPRL1/LXA4R agonists, the synthetic MMK-1 peptide and a stable analog of LXA4. Thus, a naturally produced cleaved form of uPAR is a unique endogenous chemotactic agonist for FPRL1/LXA4R receptor and its activity can be antagonized by specific ligands. These results provide the first direct link, to our knowledge, between the fibrinolytic machinery and the inflammatory response, demonstrating that uPA-derived peptide fragments can activate a specific chemotactic receptor.
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Registered trials
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.