ArticleThe Journal of biological chemistry2014
Syk and Src family kinases regulate C-type lectin receptor 2 (CLEC-2)-mediated clustering of podoplanin and platelet adhesion to lymphatic endothelial cells.
Article in The Journal of biological chemistry, 2014. 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.
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Who cites it
35 citing papers in PubMed, 86 citations in OpenAlex.
- Receptor homodimerization significantly prolongs the lifetime of ligand-induced cross-linking of CLEC-2 but not GPVI.Blood vessels, thrombosis & hemostasis · 2026Article
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Podoplanin-positive cell-derived small extracellular vesicles contribute to cardiac amyloidosis after myocardial infarction.Cell reports · 2025Article
- Advancing Platelet Research Through Live-Cell Imaging: Challenges, Techniques, and Insights.Sensors (Basel, Switzerland) · 2025Review
- The Dectin-1 and Dectin-2 clusters: C-type lectin receptors with fundamental roles in immunity.EMBO reports · 2024Review
- Lymphatic vessel: origin, heterogeneity, biological functions, and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Experimental validation of computerised models of clustering of platelet glycoprotein receptors that signal via tandem SH2 domain proteins.PLoS computational biology · 2022Article
- Katacine Is a New Ligand of CLEC-2 that Acts as a Platelet Agonist.Thrombosis and haemostasis · 2022Article
- Role of podoplanin and Kupffer cells in liver injury after ischemia-reperfusion in mice.Surgery today · 2022Article
- Platelets, Constant and Cooperative Companions of Sessile and Disseminating Tumor Cells, Crucially Contribute to the Tumor Microenvironment.Frontiers in cell and developmental biology · 2021Review
- Article
- Src family kinases inhibition by dasatinib blocks initial and subsequent platelet deposition on collagen under flow, but lacks efficacy with thrombin generation.Thrombosis research · 2020Article
- Control of Platelet CLEC-2-Mediated Activation by Receptor Clustering and Tyrosine Kinase Signaling.Biophysical journal · 2020Article
- Platelet CLEC-2 and lung development.Research and practice in thrombosis and haemostasis · 2020Review
- Kaposiform hemangioendothelioma: current knowledge and future perspectives.Orphanet journal of rare diseases · 2020Review
- Comparison of the GPVI inhibitors losartan and honokiol.Platelets · 2020Article
- Platelets and cancer-associated thrombosis: focusing on the platelet activation receptor CLEC-2 and podoplanin.Hematology. American Society of Hematology. Education Program · 2019Review
- Tspan18 is a novel regulator of the CaHaematologica · 2019Article
- Role of Platelet Glycoprotein VI and Tyrosine Kinase Syk in Thrombus Formation on Collagen-Like Surfaces.International journal of molecular sciences · 2019Article
- Regulation of cytoskeleton and adhesion signaling in osteoclasts by tetraspanin CD82.Bone reports · 2019Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 4 countries.
Funding
Abstract
The interaction of C-type lectin receptor 2 (CLEC-2) on platelets with Podoplanin on lymphatic endothelial cells initiates platelet signaling events that are necessary for prevention of blood-lymph mixing during development. In the present study, we show that CLEC-2 signaling via Src family and Syk tyrosine kinases promotes platelet adhesion to primary mouse lymphatic endothelial cells at low shear. Using supported lipid bilayers containing mobile Podoplanin, we further show that activation of Src and Syk in platelets promotes clustering of CLEC-2 and Podoplanin. Clusters of CLEC-2-bound Podoplanin migrate rapidly to the center of the platelet to form a single structure. Fluorescence lifetime imaging demonstrates that molecules within these clusters are within 10 nm of one another and that the clusters are disrupted by inhibition of Src and Syk family kinases. CLEC-2 clusters are also seen in platelets adhered to immobilized Podoplanin using direct stochastic optical reconstruction microscopy. These findings provide mechanistic insight by which CLEC-2 signaling promotes adhesion to Podoplanin and regulation of Podoplanin signaling, thereby contributing to lymphatic vasculature development.
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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.