ArticleBlood2011
S6K1 and mTOR regulate Rac1-driven platelet activation and aggregation.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.
- Genome-wide meta-analysis identifies 93 risk loci and enables risk prediction equivalent to monogenic forms of venous thromboembolism.Nature genetics · 2023Pooled it
- Treatment with acetylsalicylic acid prevents short to mid-term radiographic progression of nontraumatic osteonecrosis of the femoral head: a pilot study.Canadian journal of surgery. Journal canadien de chirurgie · 2015Trial
- Ex vivo effects of low dose delayed release rapamycin on agonist-induced platelet aggregation, activation and procoagulant platelet phenotypes in domestic cats.Scientific reports · 2026Article
- Platelet mTOR Is a Regulator of Sterile Immunothrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Platelet Autophagy as a Druggable Intracellular Pathway: Therapeutic Opportunities in Thromboinflammatory Diseases.Pharmaceutics · 2026Review
- Are Procoagulant Platelets an Emerging Therapeutic Target? A General Review with an Emphasis on Their Clinical Significance in Companion Animals.International journal of molecular sciences · 2025Review
- Evolving FATE: A New Lens on the Pathogenesis and Management of Feline Cardiogenic Arterial Thromboembolism.Animals : an open access journal from MDPI · 2025Review
- Platelet spreading and clot retraction are regulated by 2 distinct αThe Journal of pharmacology and experimental therapeutics · 2025Article
- Platelet Proteomics and Tissue Metabolomics Investigation for the Mechanism of Aspirin Eugenol Ester on Preventive Thrombosis Mechanism in a Rat Thrombosis Model.International journal of molecular sciences · 2024Article
- Microbial Heterogeneity Identification of Cerebral Thrombi Via Metagenomic Next-Generation Sequencing-Based Strategy.Journal of the American Heart Association · 2024Article
- Aging-related alterations in mechanistic target of rapamycin signaling promote platelet hyperreactivity and thrombosis.Journal of thrombosis and haemostasis : JTH · 2024Article
- Interferon Interrupted: Are P2YJACC. Basic to translational science · 2024Article
- Marine-Fungus-Derived Natural Compound 4-Hydroxyphenylacetic Acid Induces Autophagy to Exert Antithrombotic Effects in Zebrafish.Marine drugs · 2024Article
- The emerging Janus face of SVEP1 in development and disease.Trends in molecular medicine · 2023Review
- The Novel Role of Noncoding RNAs in Modulating Platelet Function: Implications in Activation and Aggregation.International journal of molecular sciences · 2023Review
- SVEP1 is an endogenous ligand for the orphan receptor PEAR1.Nature communications · 2023Article
- Article
- Platelet, Fibrinolytic and Other Coagulation Abnormalities in Newly-Diagnosed Patients with Chronic Thromboembolic Pulmonary Hypertension.Diagnostics (Basel, Switzerland) · 2022Article
- Rac Inhibition Causes Impaired GPVI Signalling in Human Platelets through GPVI Shedding and Reduction in PLCγ2 Phosphorylation.International journal of molecular sciences · 2022Article
- Rapamycin attenuated podocyte apoptosis via upregulation of nestin in Ang II-induced podocyte injury.Molecular biology reports · 2022Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Platelet activation and thrombus formation are under the control of signaling systems that integrate cellular homeostasis with cytoskeletal dynamics. Here, we identify a role for the ribosome protein S6 kinase (S6K1) and its upstream regulator mTOR in the control of platelet activation and aggregate formation under shear flow. Platelet engagement of fibrinogen initiated a signaling cascade that triggered the activation of S6K1 and Rac1. Fibrinogen-induced S6K1 activation was abolished by inhibitors of Src kinases, but not Rac1 inhibitors, demonstrating that S6K1 acts upstream of Rac1. S6K1 and Rac1 interacted in a protein complex with the Rac1 GEF TIAM1 and colocalized with actin at the platelet lamellipodial edge, suggesting that S6K1 and Rac1 work together to drive platelet spreading. Pharmacologic inhibitors of mTOR and S6K1 blocked Rac1 activation and prevented platelet spreading on fibrinogen, but had no effect on Src or FAK kinase activation. mTOR inhibitors dramatically reduced collagen-induced platelet aggregation and promoted the destabilization of platelet aggregates formed under shear flow conditions. Together, these results reveal novel roles for S6K1 and mTOR in the regulation of Rac1 activity and provide insights into the relationship between the pharmacology of the mTOR system and the molecular mechanisms of platelet activation.
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What OpenQuestion holds
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.