ArticleProceedings of the National Academy of Sciences of the United States of America2006
Disulfide isomerization switches tissue factor from coagulation to cell signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. 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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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
148 citing papers in PubMed, 336 citations in OpenAlex.
- Protein disulfide isomerase inhibition blocks thrombin generation in humans by interfering with platelet factor V activation.JCI insight · 2017Trial
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- Extracellular PDI in thrombosis and vascular injury.Thrombosis journal · 2025Review
- Venous Thromboembolism in Patients with Glioblastoma: Molecular Mechanisms and Clinical Implications.Thrombosis and haemostasis · 2025Review
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- Tumor-expressed factor VII is associated with survival and regulates tumor progression in breast cancer.Blood advances · 2023Article
- The Tissue Factor Pathway in Cancer: Overview and Role of Heparan Sulfate Proteoglycans.Cancers · 2023Review
- Targeting myeloid cell coagulation signaling blocks MAP kinase/TGF-β1-driven fibrotic remodeling in ischemic heart failure.The Journal of clinical investigation · 2023Article
- Tissue factor in cancer-associated thromboembolism: possible mechanisms and clinical applications.British journal of cancer · 2022Review
- Integrin regulation by tissue factor promotes cancer stemness and metastatic dissemination in breast cancer.Oncogene · 2022Article
- Platelet-monocyte interaction amplifies thromboinflammation through tissue factor signaling in COVID-19.Blood advances · 2022Article
- Premortem Skin Biopsy Assessing Microthrombi, Interferon Type I Antiviral and Regulatory Proteins, and Complement Deposition Correlates with Coronavirus Disease 2019 Clinical Stage.The American journal of pathology · 2022Article
- Changing Perspectives from Oxidative Stress to Redox Signaling-Extracellular Redox Control in Translational Medicine.Antioxidants (Basel, Switzerland) · 2022Review
- Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts.Cancers · 2021Article
- Recent advances in Extracellular Vesicles and their involvements in vasculitis.Free radical biology & medicine · 2021Review
- A First-In-Class, Humanized Antibody Targeting Alternatively Spliced Tissue Factor: Preclinical Evaluation in an Orthotopic Model of Pancreatic Ductal Adenocarcinoma.Frontiers in oncology · 2021Article
- [Tissue factors and venous thromboembolism in cancer patients].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2020Article
88 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Cell-surface tissue factor (TF) binds the serine protease factor VIIa to activate coagulation or, alternatively, to trigger signaling through the G protein-coupled, protease-activated receptor 2 (PAR2) relevant to inflammation and angiogenesis. Here we demonstrate that TF.VIIa-mediated coagulation and cell signaling involve distinct cellular pools of TF. The surface-accessible, extracellular Cys186-Cys209 disulfide bond of TF is critical for coagulation, and protein disulfide isomerase (PDI) disables coagulation by targeting this disulfide. A TF mutant (TF C209A) with an unpaired Cys186 retains TF.VIIa signaling activity, and it has reduced affinity for VIIa, a characteristic of signaling TF on cells with constitutive TF expression. We further show that PDI suppresses TF coagulant activity in a nitric oxide-dependent pathway, linking the regulation of TF thrombogenicity to oxidative stress in the vasculature. Furthermore, a unique monoclonal antibody recognizes only the noncoagulant, cryptic conformation of TF. This antibody inhibits formation of the TF.PAR2 complex and TF.VIIa signaling, but it does not prevent coagulation activation. These experiments delineate an upstream regulatory mechanism that controls TF function, and they provide initial evidence that TF.VIIa signaling can be specifically inhibited with minimal effects on coagulation.
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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.