ArticleThe Journal of biological chemistry2015
Distinct pathways regulate Syk protein activation downstream of immune tyrosine activation motif (ITAM) and hemITAM receptors in platelets.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 78 citations in OpenAlex.
- Article
- Comparison of variably specific Bruton tyrosine kinase inhibitors on platelet aggregation mediated by Fcγ receptor (FcγR) IIa, glycoprotein VI, and platelet endothelial aggregation receptor (PEAR) 1: implications for Bruton tyrosine kinase inhibitors as antithrombotic therapy.Research and practice in thrombosis and haemostasis · 2026Article
- The small-molecule Syk inhibitor R788 inhibits hematopoiesis and worsens anemia in sickle cell disease mice.Blood vessels, thrombosis & hemostasis · 2026Article
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Article
- Role of Liver Kinase 1B in Platelet Activation and Host Defense DuringInternational journal of molecular sciences · 2025Article
- Fucosylated Glycosaminoglycan Oligosaccharide HS14, Derived from Sea Cucumbers, Is a Novel Inhibitor of Platelet Toll-like Receptor 2.Marine drugs · 2025Article
- Molecular mechanisms driving the interactions between platelet and gastric cancer cells during peritoneal dissemination.Oncology letters · 2024Article
- Article
- Recent progress in ITP treatment.International journal of hematology · 2023Review
- Article
- TULA-Family Regulators of Platelet Activation.International journal of molecular sciences · 2022Review
- Platelets and tyrosine kinase inhibitors: clinical features, mechanisms of action, and effects on physiology.American journal of physiology. Cell physiology · 2022Review
- The GPIbα intracellular tail - role in transducing VWF- and collagen/GPVI-mediated signaling.Haematologica · 2022Article
- Clustering extent-dependent differential signaling by CLEC-2 receptors in platelets.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
- PD-L1 Regulates Platelet Activation and ThrombosisFrontiers in pharmacology · 2022Article
- Megakaryocyte-specific knockout of the Mir-99b/let7e/125a cluster lowers platelet count without altering platelet function.Blood cells, molecules & diseases · 2021Article
- Molecular Proteomics and Signalling of Human Platelets in Health and Disease.International journal of molecular sciences · 2021Review
- Assessment of the effects of Syk and BTK inhibitors on GPVI-mediated platelet signaling and function.American journal of physiology. Cell physiology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Tyrosine kinase pathways are known to play an important role in the activation of platelets. In particular, the GPVI and CLEC-2 receptors are known to activate Syk upon tyrosine phosphorylation of an immune tyrosine activation motif (ITAM) and hemITAM, respectively. However, unlike GPVI, the CLEC-2 receptor contains only one tyrosine motif in the intracellular domain. The mechanisms by which this receptor activates Syk are not completely understood. In this study, we identified a novel signaling mechanism in CLEC-2-mediated Syk activation. CLEC-2-mediated, but not GPVI-mediated, platelet activation and Syk phosphorylation were abolished by inhibition of PI3K, which demonstrates that PI3K regulates Syk downstream of CLEC-2. Ibrutinib, a Tec family kinase inhibitor, also completely abolished CLEC-2-mediated aggregation and Syk phosphorylation in human and murine platelets. Furthermore, embryos lacking both Btk and Tec exhibited cutaneous edema associated with blood-filled vessels in a typical lymphatic pattern similar to CLEC-2 or Syk-deficient embryos. Thus, our data show, for the first time, that PI3K and Tec family kinases play a crucial role in the regulation of platelet activation and Syk phosphorylation downstream of the CLEC-2 receptor.
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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.