ArticleBlood2010
Factor XII stimulates ERK1/2 and Akt through uPAR, integrins, and the EGFR to initiate angiogenesis.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 119 citations in OpenAlex.
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- Modulation of immune responses by opioids through toll-like and P2X receptor signaling in COVID-19.Purinergic signalling · 2026Review
- Inhibition of FXIIa attenuates kidney fibrosis in mice with unilateral ureteral obstruction.Cellular and molecular life sciences : CMLS · 2025Article
- Insights from the Evolution of Coagulation: A New Perspective on Anti-Inflammatory Strategies in the ICU-Focus on the Contact Activation System.Biomedicines · 2025Review
- Review
- Advancements in research on the thrombo-inflammation mechanisms mediated by factor XII in ischemic stroke.Journal of thrombosis and thrombolysis · 2025Review
- Activation of the Coagulation Cascade as a Universal Danger Sign.Current issues in molecular biology · 2025Review
- Factor XII signaling via uPAR-integrin β1 axis promotes tubular senescence in diabetic kidney disease.Nature communications · 2024Article
- Global transcriptomic network analysis of the crosstalk between microbiota and cancer-related cells in the oral-gut-lung axis.Frontiers in cellular and infection microbiology · 2024Article
- C1 inhibitor and prolylcarboxypeptidase modulate prekallikrein activation on endothelial cells.The Journal of allergy and clinical immunology · 2023Article
- PLAUR splicing pattern in hereditary angioedema patients' monocytes and macrophages.Molecular biology reports · 2023Article
- The uPA/uPAR System Orchestrates the Inflammatory Response, Vascular Homeostasis, and Immune System in Fibrosis Progression.International journal of molecular sciences · 2023Review
- The contact system in liver injury.Seminars in immunopathology · 2021Review
- Identification of Human Kinin-Forming Enzyme Inhibitors from Medicinal Herbs.Molecules (Basel, Switzerland) · 2021Article
- FXII regulates the formation of deep vein thrombosis via the PI3K/AKT signaling pathway in mice.International journal of molecular medicine · 2021Article
- Fibrinolytic System and Cancer: Diagnostic and Therapeutic Applications.International journal of molecular sciences · 2021Review
- uPAR-expressing melanoma exosomes promote angiogenesis by VE-Cadherin, EGFR and uPAR overexpression and rise of ERK1,2 signaling in endothelial cells.Cellular and molecular life sciences : CMLS · 2021Article
- Novel anti-thrombotic mechanisms mediated by Mas receptor as result of balanced activities between the kallikrein/kinin and the renin-angiotensin systems.Pharmacological research · 2020Review
- Quantifying the strength of heterointeractions among receptor tyrosine kinases from different subfamilies: Implications for cell signaling.The Journal of biological chemistry · 2020Article
- Antibody inhibition of contact factor XII reduces platelet deposition in a model of extracorporeal membrane oxygenator perfusion in nonhuman primates.Research and practice in thrombosis and haemostasis · 2020Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Factor XII (FXII) and high molecular weight kininogen (HK) mutually block each other's binding to the urokinase plasminogen activator receptor (uPAR). We investigated if FXII stimulates cells by interacting with uPAR. FXII (3-62nM) with 0.05mM Zn(2+) induces extracellular signal-related kinase 1/2 (ERK1/2; mitogen-activated protein kinase 44 [MAPK44] and MAPK42) and Akt (Ser473) phosphorylation in endothelial cells. FXII-induced phosphorylation of ERK1/2 or Akt is a zymogen activity, not an enzymatic event. ERK1/2 or Akt phosphorylation is blocked upstream by PD98059 or Wortmannin or LY294002, respectively. An uPAR signaling region for FXII is on domain 2 adjacent to uPAR's integrin binding site. Cleaved HK or peptides from HK's domain 5 blocks FXII-induced ERK1/2 and Akt phosphorylation. A beta(1) integrin peptide that binds uPAR, antibody 6S6 to beta(1) integrin, or the epidermal growth factor receptor (EGFR) inhibitor AG1478 blocks FXII-induced phosphorylation of ERK1/2 and Akt. FXII induces endothelial cell proliferation and 5-bromo-2'deoxy-uridine incorporation. FXII stimulates aortic sprouting in normal but not uPAR-deficient mouse aorta. FXII produces angiogenesis in matrigel plugs in normal but not uPAR-deficient mice. FXII knockout mice have reduced constitutive and wound-induced blood vessel number. In sum, FXII initiates signaling mediated by uPAR, beta(1) integrin, and the EGFR to induce human umbilical vein endothelial cell proliferation, growth, and angiogenesis.
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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.