ArticleNature2013
A directional switch of integrin signalling and a new anti-thrombotic strategy.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 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
103 citing papers in PubMed, 194 citations in OpenAlex.
- A scalable high-throughput platform for the discovery of intracellular and extracellular regulators of platelet migration.Blood advances · 2026Article
- IGF1 Binding to Integrin αvβ3 Induces Direct Gα13 Binding to IGF1R Kinase.International journal of molecular sciences · 2026Article
- Qiliqiangxin capsule attenuates platelet activation and thrombosis by suppressing CaThrombosis journal · 2026Article
- Direct Binding of Lyn to GPIbβ Transmits 2-Way GPIb-IX Signaling to Stimulate Platelet Activation and VWF Binding.Circulation research · 2025Article
- α-Actinin-1 in Megakaryocytes: Its Structure, Interacting Proteins and Implications for Thrombopoiesis.Biomedicines · 2025Review
- A Novel KGD-Based αIIbβ3 Antagonist Prevents Arterial Thrombosis While Preserving Hemostasis and Avoiding Thrombocytopenia.International journal of molecular sciences · 2025Article
- The gut microbiota-bile acid-TGR5 axis orchestrates platelet activation and atherothrombosis.Nature cardiovascular research · 2025Article
- NR4A1 Acts as a Novel Regulator of Platelet Activation and Thrombus Formation.Circulation research · 2025Article
- The impact of a high fat diet and platelet activation on pre-metastatic niche formation.Nature communications · 2025Article
- Intermittent fasting inhibits platelet activation and thrombosis through the intestinal metabolite indole-3-propionate.Life metabolism · 2025Article
- A nonactivatingBlood vessels, thrombosis & hemostasis · 2025Article
- Iloprost Concentration-Dependently Attenuates Platelet Function and Apoptosis by Elevating PKA Activity.Journal of cellular and molecular medicine · 2025Article
- Biochemical and biophysical mechanisms macrophages use to tune phagocytic appetite.Journal of cell science · 2025Review
- Multi-parametric thrombus profiling microfluidics detects intensified biomechanical thrombogenesis associated with hypertension and aging.Nature communications · 2024Article
- Multi-parametric thrombus profiling microfluidics detects intensified biomechanical thrombogenesis associated with hypertension and aging.bioRxiv : the preprint server for biology · 2024Article
- Contributions of the individual domains of αCytoskeleton (Hoboken, N.J.) · 2024Article
- Mechanism of Bile Acid in Regulating Platelet Function and Thrombotic Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- GPCR-Gα13 Involvement in Mitochondrial Function, Oxidative Stress, and Prostate Cancer.International journal of molecular sciences · 2024Review
- Integrins as Drug Targets in Vascular and Related Diseases.International journal of drug discovery and pharmacology · 2024Article
- Roles of Integrin in Cardiovascular Diseases: From Basic Research to Clinical Implications.International journal of molecular sciences · 2024Review
43 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Integrins have a critical role in thrombosis and haemostasis. Antagonists of the platelet integrin αIIbβ3 are potent anti-thrombotic drugs, but also have the life-threatening adverse effect of causing bleeding. It is therefore desirable to develop new antagonists that do not cause bleeding. Integrins transmit signals bidirectionally. Inside-out signalling activates integrins through a talin-dependent mechanism. Integrin ligation mediates thrombus formation and outside-in signalling, which requires Gα13 and greatly expands thrombi. Here we show that Gα13 and talin bind to mutually exclusive but distinct sites within the integrin β3 cytoplasmic domain in opposing waves. The first talin-binding wave mediates inside-out signalling and also ligand-induced integrin activation, but is not required for outside-in signalling. Integrin ligation induces transient talin dissociation and Gα13 binding to an EXE motif (in which X denotes any residue), which selectively mediates outside-in signalling and platelet spreading. The second talin-binding wave is associated with clot retraction. An EXE-motif-based inhibitor of Gα13-integrin interaction selectively abolishes outside-in signalling without affecting integrin ligation, and suppresses occlusive arterial thrombosis without affecting bleeding time. Thus, we have discovered a new mechanism for the directional switch of integrin signalling and, on the basis of this mechanism, designed a potent new anti-thrombotic drug that does not cause bleeding.
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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.