ArticleBlood2009
Antithrombotic effects of targeting alphaIIbbeta3 signaling in platelets.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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.
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.
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Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
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- Integrin αvβ3 Upregulation in Response to Nutrient Stress Promotes Lung Cancer Cell Metabolic Plasticity.Cancer research · 2024Article
- Structure, signal transduction, activation, and inhibition of integrin αIIbβ3.Thrombosis journal · 2023Review
- Pharmacological Actions of 5-Hydroxyindolin-2 on Modulation of Platelet Functions and Thrombus Formation via Thromboxane AInternational journal of molecular sciences · 2022Article
- Review
- Targeting the RT loop of Src SH3 in Platelets Prevents Thrombosis without Compromising Hemostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Fluorescent Imaging-Guided Chemo- and Photodynamic Therapy of Hepatocellular Carcinoma with HCPT@NMOFs-RGD Nanocomposites.International journal of nanomedicine · 2022Article
- Paxillin binding to the PH domain of kindlin-3 in platelets is required to support integrin αIIbβ3 outside-in signaling.Journal of thrombosis and haemostasis : JTH · 2021Article
- Itgb3-integrin-deficient mice may not be a sufficient model for patients with Glanzmann thrombasthenia.Molecular medicine reports · 2021Article
- The (Patho)Biology of SRC Kinase in Platelets and Megakaryocytes.Medicina (Kaunas, Lithuania) · 2020Review
- uPAR isoform 2 forms a dimer and induces severe kidney disease in mice.The Journal of clinical investigation · 2019Article
- Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting.Journal of hematology & oncology · 2019Review
- Integrin αBlood · 2017Review
- New Concepts and Mechanisms of Platelet Activation Signaling.Physiology (Bethesda, Md.) · 2017Review
- Toward correlating structure and mechanics of platelets.Cell adhesion & migration · 2016Review
- Roles of integrin β3 cytoplasmic tail in bidirectional signal transduction in a trans-dominant inhibition model.Frontiers of medicine · 2016Article
- Article
- Integrin beta-3 genetic variants and risk of venous thromboembolism in colorectal cancer patients.Thrombosis research · 2015Article
- The Tyrosine Kinase c-Src Specifically Binds to the Active Integrin αIIbβ3 to Initiate Outside-in Signaling in Platelets.The Journal of biological chemistry · 2015Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
alphaIIbbeta3 interaction with fibrinogen promotes Src-dependent platelet spreading in vitro. To determine the consequences of this outside-in signaling pathway in vivo, a "beta3(Delta760-762)" knockin mouse was generated that lacked the 3 C-terminal beta3 residues (arginine-glycine-threonine [RGT]) necessary for alphaIIbbeta3 interaction with c-Src, but retained beta3 residues necessary for talin-dependent fibrinogen binding. beta3(Delta760-762) mice were compared with wild-type beta3(+/+) littermates, beta3(+/-) heterozygotes, and knockin mice where beta3 RGT was replaced by beta1 C-terminal cysteine-glycine-lysine (EGK) to potentially enable signaling by Src kinases other than c-Src. Whereas beta3(+/+), beta3(+/-) and beta3/beta1(EGK) platelets spread and underwent tyrosine phosphorylation normally on fibrinogen, beta3(Delta760-762) platelets spread poorly and exhibited reduced tyrosine phosphorylation of c-Src substrates, including beta3 (Tyr(747)). Unlike control mice, beta3(Delta760-762) mice were protected from carotid artery thrombosis after vessel injury with FeCl(3). Some beta3(Delta760-762) mice exhibited prolonged tail bleeding times; however, none demonstrated spontaneous bleeding, excess bleeding after surgery, fecal blood loss, or anemia. Fibrinogen binding to beta3(Delta760-762) platelets was normal in response to saturating concentrations of protease-activated receptor 4 or glycoprotein VI agonists, but responses to adenosine diphosphate were impaired. Thus, deletion of beta3 RGT disrupts c-Src-mediated alphaIIbbeta3 signaling and confers protection from arterial thrombosis. Consequently, targeting alphaIIbbeta3 signaling may represent a feasible antithrombotic strategy.
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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.