ArticleBlood2015
The N-terminal SH2 domain of Syk is required for (hem)ITAM, but not integrin, signaling in mouse platelets.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 55 citations in OpenAlex.
- Megakaryocytes Internalize and Are Activated by Immune Complexes.Circulation research · 2026Article
- Microglial ITAM & ITIM Signaling in Neurodegenerative Disease and Brain Aging.Journal of molecular biology · 2026Review
- When GPVI Goes Rogue: Pathogenesis and Therapeutic Horizons in ITP.Expert reviews in molecular medicine · 2026Review
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Discovery of Carbonic Anhydrase 9 as a Novel CLEC2 Ligand in a Cellular Interactome Screen.Cells · 2024Article
- The podoplanin-CLEC-2 interaction promotes platelet-mediated melanoma pulmonary metastasis.BMC cancer · 2024Article
- Divalent nanobodies to platelet CLEC-2 can serve as agonists or antagonists.Communications biology · 2023Article
- Treatment of congenital thrombocytopenia and decreased collagen reactivity in G6b-B-deficient mice.Blood advances · 2023Article
- Insulin-regulated aminopeptidase contributes to setting the intensity of FcR-mediated inflammation.Frontiers in immunology · 2022Article
- Molecular Proteomics and Signalling of Human Platelets in Health and Disease.International journal of molecular sciences · 2021Review
- mTOR regulates GPVI-mediated platelet activation.Journal of translational medicine · 2021Article
- Low-dose Btk inhibitors selectively block platelet activation by CLEC-2.Haematologica · 2021Article
- Control of Platelet CLEC-2-Mediated Activation by Receptor Clustering and Tyrosine Kinase Signaling.Biophysical journal · 2020Article
- Integrin-associated molecules and signalling cross talking in osteoclast cytoskeleton regulation.Journal of cellular and molecular medicine · 2020Review
- Identification of Inhibitors of Integrin Cytoplasmic Domain Interactions With Syk.Frontiers in immunology · 2020Article
- Overview of RAW264.7 for osteoclastogensis study: Phenotype and stimuli.Journal of cellular and molecular medicine · 2019Review
- Comparative Analysis of Microfluidics Thrombus Formation in Multiple Genetically Modified Mice: Link to Thrombosis and Hemostasis.Frontiers in cardiovascular medicine · 2019Article
- Immobilized fibrinogen activates human platelets through glycoprotein VI.Haematologica · 2018Article
- Phosphorylated immunoreceptor tyrosine-based activation motifs and integrin cytoplasmic domains activate spleen tyrosine kinase via distinct mechanisms.The Journal of biological chemistry · 2018Article
- The podoplanin-CLEC-2 axis inhibits inflammation in sepsis.Nature communications · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
We have used a novel knockin mouse to investigate the effect of disruption of phosphotyrosine binding of the N-terminal SH2 domain of Syk on platelet activation by GPVI, CLEC-2, and integrin αIIbβ3. The Syk(R41Afl/fl) mouse was crossed to a PF4-Cre(+) mouse to induce expression of the Syk mutant in the megakaryocyte/platelet lineage. Syk(R41Afl/fl;PF4-Cre) mice are born at approximately 50% of the expected frequency and have a similar phenotype to Syk(fl/fl;PF4-Cre) mice, including blood-lymphatic mixing and chyloascites. Anastomosis of the venous and lymphatic vasculatures can be seen in the mesenteric circulation accounting for rapid and continuous mixing of the 2 vasculatures. Platelet activation by CLEC-2 and GPVI is abolished in Syk(R41Afl/fl;PF4-Cre) platelets. Syk phosphorylation on Tyr519/20 is blocked in CLEC-2-stimulated platelets, suggesting a model in which binding of Syk via its N-terminal SH2 domain regulates autophosphorylation. In contrast, outside-in signaling by integrin αIIbβ3 is not altered, but it is inhibited in the presence of inhibitors of Src and Syk tyrosine kinases. These results demonstrate that αIIbβ3 regulates Syk through an ITAM-independent pathway in mice and provide novel insight into the course of events underlying Syk activation and hemITAM phosphorylation by CLEC-2.
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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.