ArticleThe Journal of clinical investigation2009
Lack of protein S in mice causes embryonic lethal coagulopathy and vascular dysgenesis.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
What it found
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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
101 citing papers in PubMed, 169 citations in OpenAlex.
- Structural organization of TAM receptor ectodomains.The Biochemical journal · 2026Article
- MERTK inhibition cooperates with immunomodulatory cyclophosphamide to induce CXCL9⁺ monocyte-macrophage programming and durable antitumor immunity in triple negative breast cancer.Cancer immunology research · 2026Article
- A long first intron of PROS1 modulates protein S expression across tissues in mice and humans.Blood advances · 2026Article
- Protein S: a vitamin K-dependent factor bridging haemostasis, tissue homeostasis and cancer.The Biochemical journal · 2026Review
- MERTK inhibition cooperates with immunomodulatory cyclophosphamide to induce CXCL9bioRxiv : the preprint server for biology · 2026Article
- From pathogenesis to therapeutic targeting: new insight into TAM receptors in rheumatoid arthritis.Cell & bioscience · 2025Review
- Estrogen and obesity synergistically suppress protein S via HIF1α, enhancing thrombosis potential.The Journal of clinical investigation · 2025Article
- Recent advances in TAM mechanisms in lung diseases.Journal of translational medicine · 2025Review
- Loss of protein C vs protein S results in discrepant thrombotic phenotypes.Blood advances · 2025Article
- SARS-CoV-2 Vaccine Improved Hemostasis of a Patient with Protein S Deficiency: A Case Report.International journal of molecular sciences · 2024Article
- Role and Mechanisms of Tyro3 in Podocyte Biology and Glomerular Disease.Kidney diseases (Basel, Switzerland) · 2024Review
- Vitamin K2 Supplementation in Hospitalised COVID-19 Patients: A Randomised Controlled Trial.Journal of clinical medicine · 2024Article
- In the Eyes of the Beholder-NewInternational journal of molecular sciences · 2024Review
- Exploring nonreplacement therapies' impact on hemophilia and other rare bleeding disorders.Research and practice in thrombosis and haemostasis · 2024Article
- The Vitamin K-Dependent Anticoagulant Factor, Protein S, Regulates Vascular Permeability.Current issues in molecular biology · 2024Article
- The TAM Subfamily of Receptor Tyrosine Kinases: The Early Years.International journal of molecular sciences · 2024Review
- Therapeutic targeting of the functionally elusive TAM receptor family.Nature reviews. Drug discovery · 2024Review
- TFPIα anticoagulant function is highly dependent on protein S in vivo.Science advances · 2024Article
- Tyro3 promotes the maturation of glutamatergic synapses.Frontiers in neuroscience · 2024Article
- TAM family kinases as therapeutic targets at the interface of cancer and immunity.Nature reviews. Clinical oncology · 2023Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Protein S (ProS) is a blood anticoagulant encoded by the Pros1 gene, and ProS deficiencies are associated with venous thrombosis, stroke, and autoimmunity. These associations notwithstanding, the relative risk that reduced ProS expression confers in different disease settings has been difficult to assess without an animal model. We have now described a mouse model of ProS deficiency and shown that all Pros1-/- mice die in utero,from a fulminant coagulopathy and associated hemorrhages. Although ProS is known to act as a cofactor for activated Protein C (aPC), plasma from Pros1+/- heterozygous mice exhibited accelerated thrombin generation independent of aPC, and Pros1 mutants displayed defects in vessel development and function not seen in mice lacking protein C. Similar vascular defects appeared in mice in which Pros1 was conditionally deleted in vascular smooth muscle cells. Mutants in which Pros1 was deleted specifically in hepatocytes, which are thought to be the major source of ProS in the blood, were viable as adults and displayed less-severe coagulopathy without vascular dysgenesis. Finally, analysis of mutants in which Pros1 was deleted in endothelial cells indicated that these cells make a substantial contribution to circulating ProS. These results demonstrate that ProS is a pleiotropic anticoagulant with aPC-independent activities and highlight new roles for ProS in vascular development and homeostasis.
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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.