ArticleBlood2015
SLAP/SLAP2 prevent excessive platelet (hem)ITAM signaling in thrombosis and ischemic stroke in mice.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 31 citations in OpenAlex.
- Isaridin E Attenuates Ischemic Brain Injury in Mice by Concurrently Reducing Platelet Hyperactivity and Microglial Neuroinflammation Associated with LRP1.Marine drugs · 2026Article
- Platelets and diseases: signal transduction and advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- Infarct growth precedes cerebral thrombosis following experimental stroke in mice.Scientific reports · 2021Article
- A Role of the Podoplanin-CLEC-2 Axis in Promoting Inflammatory Response After Ischemic Stroke in Mice.Neurotoxicity research · 2021Article
- NADPH Oxidases Are Required for Full Platelet Activation In Vitro and Thrombosis In Vivo but Dispensable for Plasma Coagulation and Hemostasis.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- The Role of CLEC-2 and Its Ligands in Thromboinflammation.Frontiers in immunology · 2021Review
- BIN2 orchestrates platelet calcium signaling in thrombosis and thrombo-inflammation.The Journal of clinical investigation · 2020Article
- CD84 Links T Cell and Platelet Activity in Cerebral Thrombo-Inflammation in Acute Stroke.Circulation research · 2020Article
- The choline transporter Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial function.Nature communications · 2020Article
- Targeting Platelet GPVI Plus rt-PA Administration but Not α2β1-Mediated Collagen Binding Protects against Ischemic Brain Damage in Mice.International journal of molecular sciences · 2019Article
- Platelets as Modulators of Cerebral Ischemia/Reperfusion Injury.Frontiers in immunology · 2019Review
- GPVI signaling is compromised in newly formed platelets after acute thrombocytopenia in mice.Blood · 2018Article
- Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation.Platelets · 2017Article
- Sex-Specific Associations between Particulate Matter Exposure and Gene Expression in Independent Discovery and Validation Cohorts of Middle-Aged Men and Women.Environmental health perspectives · 2017Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
Glycoprotein VI and C-type lectin-like receptor 2 are essential platelet activating receptors in hemostasis and thrombo-inflammatory disease, which signal through a (hem)immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway. The adapter molecules Src-like adapter proteins (SLAP and SLAP2) are involved in the regulation of immune cell surface expression and signaling, but their function in platelets is unknown. In this study, we show that platelets expressed both SLAP isoforms and that overexpression of either protein in a heterologous cell line almost completely inhibited glycoprotein VI and C-type lectin-like receptor 2 signaling. In mice, single deficiency of SLAP or SLAP2 had only moderate effects on platelet function, whereas double deficiency of both adapters resulted in markedly increased signal transduction, integrin activation, granule release, aggregation, procoagulant activity, and thrombin generation in response to (hem)ITAM-coupled, but not G protein-coupled, receptor activation. In vivo, constitutive SLAP/SLAP2 knockout mice displayed accelerated occlusive arterial thrombus formation and a dramatically worsened outcome after focal cerebral ischemia. This was attributed to the absence of both adapter proteins in platelets, as demonstrated by adoptive transfer of Slap(-/-)/Slap2(-/-) platelets into wild-type mice. Our results establish SLAP and SLAP2 as critical inhibitors of platelet (hem)ITAM signaling in the setting of arterial thrombosis and ischemic stroke.
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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.