ArticleBlood2015
Targeted downregulation of platelet CLEC-2 occurs through Syk-independent internalization.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Platelet CLEC-2 activation leads to GPIb⍺ shedding: Implications for doxorubicin chemotherapy and thrombosis.The Journal of biological chemistry · 2026Article
- The Adverse Impact of Tyrosine Kinase Inhibitors on Wound Healing and Repair.International wound journal · 2025Review
- Unraveling the enigma: housekeeping geneFrontiers in psychiatry · 2024Article
- Article
- Dasatinib Ointment Promotes Healing of Murine Excisional Skin Wound.ACS pharmacology & translational science · 2023Article
- Antibody-mediated depletion of human CLEC-2 in a novel humanized mouse model.Blood advances · 2023Article
- New insights of platelet endocytosis and its implication for platelet function.Frontiers in cardiovascular medicine · 2023Review
- Article
- Platelet-HIV: interactions and their implications.Platelets · 2022Article
- Foudroyant cerebral venous (sinus) thrombosis triggered through CLEC-2 and GPIIb/IIIa dependent platelet activation.Nature cardiovascular research · 2022Article
- Therapeutic targets and signaling mechanisms of dasatinib activity against radiation skin ulcer.Frontiers in public health · 2022Article
- Lymphatic blood filling in CLEC-2-deficient mouse models.Platelets · 2021Article
- Hemostasis vs. homeostasis: Platelets are essential for preserving vascular barrier function in the absence of injury or inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Plasma soluble C-type lectin-like receptor-2 is associated with the risk of coronary artery disease.Frontiers of medicine · 2020Article
- Overview of General and Discriminating Markers of Differential Microglia Phenotypes.Frontiers in cellular neuroscience · 2020Article
- Functional significance of the platelet immune receptors GPVI and CLEC-2.The Journal of clinical investigation · 2019Review
- Role of platelets and platelet receptors in cancer metastasis.Journal of hematology & oncology · 2018Review
- Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation.Nature communications · 2018Article
- Article
- The ins and outs of endocytic trafficking in platelet functions.Current opinion in hematology · 2017Review
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Platelet aggregation at sites of vascular injury is not only essential for hemostasis, but may also cause acute ischemic disease states such as myocardial infarction or stroke. The hemi-immunoreceptor tyrosine-based activation motif-containing C-type lectinlike receptor 2 (CLEC-2) mediates powerful platelet activation through a Src- and spleen tyrosine kinase (Syk)-dependent tyrosine phosphorylation cascade. Thereby, CLEC-2 not only contributes to thrombus formation and stabilization but also plays a central role in blood-lymphatic vessel development, tumor metastasis, and prevention of inflammatory bleeding, making it a potential pharmacologic target to modulate these processes. We have previously shown that injection of the anti-CLEC-2 antibody, INU1, results in virtually complete immunodepletion of platelet CLEC-2 in mice, which is, however, preceded by a severe transient thrombocytopenia thereby limiting its potential therapeutic use. The mechanisms underlying this targeted CLEC-2 downregulation have remained elusive. Here, we show that INU1-induced CLEC-2 immunodepletion occurs through Src-family kinase-dependent receptor internalization in vitro and in vivo, presumably followed by intracellular degradation. In mice with platelet-specific Syk deficiency, INU1-induced CLEC-2 internalization/degradation was fully preserved whereas the associated thrombocytopenia was largely prevented. These results show for the first time that CLEC-2 can be downregulated from the platelet surface through internalization in vitro and in vivo and that this can be mechanistically uncoupled from the associated antibody-induced thrombocytopenia.
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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.