ArticleThe Journal of experimental medicine2010
A novel interaction between FlnA and Syk regulates platelet ITAM-mediated receptor signaling and function.
Article in The Journal of experimental medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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
60 citing papers in PubMed, 120 citations in OpenAlex.
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- F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in platelets.Nature communications · 2025Article
- New insights of glycoprotein Ib-IX-V complex organization and glycoprotein Ibα in platelet biogenesis.Current opinion in hematology · 2024Review
- Filamin A regulates platelet shape change and contractile force generation via phosphorylation of the myosin light chain.The Biochemical journal · 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
- Tropomodulin1 exacerbates inflammatory response in macrophages by negatively regulating LPS-induced TLR4 endocytosis.Cellular and molecular life sciences : CMLS · 2024Article
- Is glycoprotein VI involved in contractual negotiations?Research and practice in thrombosis and haemostasis · 2024Article
- PACSIN2 regulates platelet integrin β1 hemostatic function.Journal of thrombosis and haemostasis : JTH · 2023Article
- A novel association between platelet filamin A and soluble N-ethylmaleimide sensitive factor attachment proteins regulates granule secretion.Research and practice in thrombosis and haemostasis · 2023Article
- Thymosin β4 is essential for thrombus formation by controlling the G-actin/F-actin equilibrium in platelets.Haematologica · 2022Article
- A gain-of-function filamin A mutation in mouse platelets induces thrombus instability.Journal of thrombosis and haemostasis : JTH · 2022Article
- The impact of aberrant von Willebrand factor-GPIbα interaction on megakaryopoiesis and platelets in humanized type 2B von Willebrand disease model mouse.Haematologica · 2022Article
- Signaling mechanisms of the platelet glycoprotein Ib-IX complex.Platelets · 2022Review
- The GPIb-IX complex on platelets: insight into its novel physiological functions affecting immune surveillance, hepatic thrombopoietin generation, platelet clearance and its relevance for cancer development and metastasis.Experimental hematology & oncology · 2022Review
- Review
- New insights into regulation of αIIbβ3 integrin signaling by filamin A.Research and practice in thrombosis and haemostasis · 2022Article
- Filamin A in platelets: Bridging the (signaling) gap between the plasma membrane and the actin cytoskeleton.Frontiers in molecular biosciences · 2022Review
- Genetic Labeling of Cells Allows Identification and Tracking of Transgenic Platelets in Mice.International journal of molecular sciences · 2021Article
- Stress response in periodontal ligament stem cells may contribute to bisphosphonate‑associated osteonecrosis of the jaw: A gene expression array analysis.Molecular medicine reports · 2020Article
- Dynamin 2 is required for GPVI signaling and platelet hemostatic function in mice.Haematologica · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Filamin A (FlnA) cross-links actin filaments and connects the Von Willebrand factor receptor GPIb-IX-V to the underlying cytoskeleton in platelets. Because FlnA deficiency is embryonic lethal, mice lacking FlnA in platelets were generated by breeding FlnA(loxP/loxP) females with GATA1-Cre males. FlnA(loxP/y) GATA1-Cre males have a macrothrombocytopenia and increased tail bleeding times. FlnA-null platelets have decreased expression and altered surface distribution of GPIbalpha because they lack the normal cytoskeletal linkage of GPIbalpha to underlying actin filaments. This results in approximately 70% less platelet coverage on collagen-coated surfaces at shear rates of 1,500/s, compared with wild-type platelets. Unexpectedly, however, immunoreceptor tyrosine-based activation motif (ITAM)- and ITAM-like-mediated signals are severely compromised in FlnA-null platelets. FlnA-null platelets fail to spread and have decreased alpha-granule secretion, integrin alphaIIbbeta3 activation, and protein tyrosine phosphorylation, particularly that of the protein tyrosine kinase Syk and phospholipase C-gamma2, in response to stimulation through the collagen receptor GPVI and the C-type lectin-like receptor 2. This signaling defect was traced to the loss of a novel FlnA-Syk interaction, as Syk binds to FlnA at immunoglobulin-like repeat 5. Our findings reveal that the interaction between FlnA and Syk regulates ITAM- and ITAM-like-containing receptor signaling and platelet function.
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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.