ArticleJournal of thrombosis and haemostasis : JTH2018
PDK1 governs thromboxane generation and thrombosis in platelets by regulating activation of Raf1 in the MAPK pathway.
Article in Journal of thrombosis and haemostasis : JTH, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
37 citing papers in PubMed, 49 citations in OpenAlex.
- Review
- Immobilized IgG-containing immune complexes require platelets to recruit neutrophils during inflammation.The Journal of clinical investigation · 2026Article
- Evaluation of D-Dimer, P-Selectin, and miR-17-5p Expression in ICU and Non-ICU COVID-19 Patients: A Cross-sectional Study.Biochemical genetics · 2026Article
- Limited availability of variant-specific germ line data creates challenges in the interpretation of myeloid NGS panels.Blood vessels, thrombosis & hemostasis · 2026Article
- Dicer Neosynthesis Regulates Platelet Reactivity: A Mechanism Altered in Type 2 Diabetes.Circulation research · 2025Article
- Mitochondrial Calcium Uniporter Regulates ITAM-Dependent Platelet Activation.Circulation research · 2025Article
- Antithrombotic Effect ofInternational journal of molecular sciences · 2025Article
- 3-Phosphoinositide-Dependent Kinase 1 as a Therapeutic Target for Treating Diabetes.Current diabetes reviews · 2025Review
- COVID-19: a vascular nightmare unfolding.Frontiers in immunology · 2025Review
- Capturing Autoinhibited PDK1 Reveals the Linker's Regulatory Role, Informing Innovative Inhibitor Design.Journal of chemical information and modeling · 2024Article
- Brevianamide F Exerts Antithrombotic Effects by Modulating the MAPK Signaling Pathway and Coagulation Cascade.Marine drugs · 2024Article
- How Protein Depletion Balances Thrombosis and Bleeding Risk in the Context of Platelet's Activatory and Negative Signaling.International journal of molecular sciences · 2024Review
- Aging-related alterations in mechanistic target of rapamycin signaling promote platelet hyperreactivity and thrombosis.Journal of thrombosis and haemostasis : JTH · 2024Article
- Antiplatelet and Antithrombotic Properties of Compound L-36, a 6H-1,3,4-Thiadiazine Derivative.Bulletin of experimental biology and medicine · 2024Article
- Targeting CRAF kinase in anti-cancer therapy: progress and opportunities.Molecular cancer · 2023Review
- Crosstalk between Platelets and SARS-CoV-2: Implications in Thrombo-Inflammatory Complications in COVID-19.International journal of molecular sciences · 2023Review
- Network pharmacology prediction and molecular docking-based strategy to discover the potential pharmacological mechanism of Huang-Qi-Gui-Zhi-Wu-Wu decoction against deep vein thrombosis.Journal of orthopaedic surgery and research · 2023Article
- Metabolic alterations upon SARS-CoV-2 infection and potential therapeutic targets against coronavirus infection.Signal transduction and targeted therapy · 2023Review
- Dematin Regulates Calcium Mobilization, Thrombosis, and Early Akt Activation in Platelets.Molecular and cellular biology · 2023Article
- Article
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Essentials Phosphoinositide 3-kinase and MAPK pathways crosstalk via PDK1. PDK1 is required for adenosine diphosphate-induced platelet activation and thromboxane generation. PDK1 regulates RAF proto-oncogene Ser/Thr kinase (Raf1) activation in the MAPK pathway. Genetic ablation of PDK1 protects against platelet-dependent thrombosis in vivo. SUMMARY: Background Platelets are dynamic effector cells with functions that span hemostatic, thrombotic and inflammatory continua. Phosphoinositide-dependent protein kinase 1 (PDK1) regulates protease-activated receptor 4-induced platelet activation and thrombus formation through glycogen synthase kinase3β. However, whether PDK1 also signals through the ADP receptor and its functional importance in vivo remain unknown. Objective To establish the mechanism of PDK1 in ADP-induced platelet activation and thrombosis. Methods We assessed the role of PDK1 on 2MeSADP-induced platelet activation by measuring aggregation, thromboxane generation and phosphorylation events in the presence of BX-795, which inhibits PDK1, or by using platelet-specific PDK1 knockout mice and performing western blot analysis. PDK1 function in thrombus formation was assessed with an in vivo pulmonary embolism model. Results PDK1 inhibition with BX-795 reduced 2-methylthio-ADP (2MeSADP)-induced aggregation of human and murine platelets by abolishing thromboxane generation. Similar results were observed in pdk1
Indexed as
Identifiers
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.