ArticleBlood2013
Platelet-derived ERp57 mediates platelet incorporation into a growing thrombus by regulation of the αIIbβ3 integrin.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 97 citations in OpenAlex.
- Hemostatic and platelet proteins are associated with bleeding grade and time to major bleed in hemato-oncological patients.Blood vessels, thrombosis & hemostasis · 2026Article
- Extracellular PDI in thrombosis and vascular injury.Thrombosis journal · 2025Review
- Mechanochemistry: Fundamental Principles and Applications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Endoplasmic reticulum protein 29 negatively regulates platelet functions and thrombosis in mice.Thrombosis journal · 2025Article
- Development of Zafirlukast Analogues for Improved Antithrombotic Activity Through Thiol Isomerase Inhibition.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Recent advances in vascular thiol isomerases: insights into structures, functions in thrombosis and antithrombotic inhibitor development.Thrombosis journal · 2025Review
- Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes.Nature communications · 2025Article
- Thiol isomerase ERp18 enhances platelet activation and arterial thrombosis.Research and practice in thrombosis and haemostasis · 2025Article
- The protein disulfide isomerase A3 and osteopontin axis promotes influenza-induced lung remodelling.British journal of pharmacology · 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
- Recent advances in vascular thiol isomerases and redox systems in platelet function and thrombosis.Journal of thrombosis and haemostasis : JTH · 2024Review
- Transmembrane thiol isomerase TMX1 counterbalances the effect of ERp46 to inhibit platelet activation and integrin αIIbβ3 function.Research and practice in thrombosis and haemostasis · 2024Article
- Protein disulfide isomerase is essential for spermatogenesis in mice.JCI insight · 2024Article
- Protein disulfide isomerase A1 regulates fenestration dynamics in primary mouse liver sinusoidal endothelial cells (LSECs).Redox biology · 2024Article
- Thioredoxin-related transmembrane protein 1 negatively regulates coagulation and phosphatidylserine exposure.Research and practice in thrombosis and haemostasis · 2024Article
- The role of heat shock proteins in the pathogenesis of heart failure (Review).International journal of molecular medicine · 2023Review
- Thrombotic Alterations under Perinatal Hypoxic Conditions: HIF and Other Hypoxic Markers.International journal of molecular sciences · 2023Review
- Endoplasmic reticulum protein 5 attenuates platelet endoplasmic reticulum stress and secretion in a mouse model.Blood advances · 2023Article
- Structure, signal transduction, activation, and inhibition of integrin αIIbβ3.Thrombosis journal · 2023Review
- PDIA3/ERp57 promotes a matrix-rich secretome that stimulates fibroblast adhesion through CCN2.American journal of physiology. Cell physiology · 2022Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 6 institutions in 4 countries.
Funding
Abstract
The platelet protein disulfide isomerase called ERp57 mediates platelet aggregation, but its role in thrombus formation is unknown. To determine the specific role of platelet-derived ERp57 in hemostasis and thrombosis, we generated a megakaryocyte/platelet-specific knockout. Despite normal platelet counts and platelet glycoprotein expression, mice with ERp57-deficient platelets had prolonged tail-bleeding times and thrombus occlusion times with FeCl3-induced carotid artery injury. Using a mesenteric artery thrombosis model, we found decreased incorporation of ERp57-deficient platelets into a growing thrombus. Platelets lacking ERp57 have defective activation of the αIIbβ3 integrin and platelet aggregation. The defect in aggregation was corrected by the addition of exogenous ERp57, implicating surface ERp57 in platelet aggregation. Using mutants of ERp57, we demonstrate the second active site targets a platelet surface substrate to potentiate platelet aggregation. Binding of Alexa 488-labeled ERp57 to thrombin-activated and Mn(2+)-treated platelets lacking β3 was decreased substantially, suggesting a direct interaction of ERp57 with αIIbβ3. Surface expression of ERp57 protein and activity in human platelets increased with platelet activation, with protein expression occurring in a physiologically relevant time frame. In conclusion, platelet-derived ERp57 directly interacts with αIIbβ3 during activation of this receptor and is required for incorporation of platelets into a growing thrombus.
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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.