ArticleJournal of thrombosis and haemostasis : JTH2008
Differential roles for the adapters Gads and LAT in platelet activation by GPVI and CLEC-2.
Article in Journal of thrombosis and haemostasis : JTH, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 39 citations in OpenAlex.
- Platelet-derived mitochondrial transfer in cancer metastasis: mechanisms, functional consequences, and translational opportunities.Clinical & experimental metastasis · 2026Review
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Sepsis-induced immunothrombosis: from cellular crosstalk to multiple organ dysfunction.Frontiers in immunology · 2026Review
- The LAT Rheostat as a Regulator of Megakaryocyte Activation.Thrombosis and haemostasis · 2024Article
- Review
- Emerging roles of platelets in cancer biology and their potential as therapeutic targets.Frontiers in oncology · 2022Review
- Plasma soluble C-type lectin-like receptor-2 is associated with the risk of coronary artery disease.Frontiers of medicine · 2020Article
- Role of platelets and platelet receptors in cancer metastasis.Journal of hematology & oncology · 2018Review
- Platelet Signaling and Disease: Targeted Therapy for Thrombosis and Other Related Diseases.Pharmacological reviews · 2018Review
- New Concepts and Mechanisms of Platelet Activation Signaling.Physiology (Bethesda, Md.) · 2017Review
- Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation.American journal of physiology. Cell physiology · 2016Article
- Akt and mitogen-activated protein kinase enhance C-type lectin-like receptor 2-mediated platelet activation by inhibition of glycogen synthase kinase 3α/β.Journal of thrombosis and haemostasis : JTH · 2015Article
- C-type lectin like receptor 2 (CLEC-2) signals independently of lipid raft microdomains in platelets.Biochemical pharmacology · 2015Article
- The N-terminal SH2 domain of Syk is required for (hem)ITAM, but not integrin, signaling in mouse platelets.Blood · 2015Article
- Emerging Roles for Platelets in Inflammation and Disease.Journal of infectious disease and therapy · 2014Article
- Reactive oxygen species play a critical role in collagen-induced platelet activation via SHP-2 oxidation.Antioxidants & redox signaling · 2014Article
- Platelet immunoreceptor tyrosine-based activation motif (ITAM) signaling and vascular integrity.Circulation research · 2014Review
- Growth factor receptor-bound protein 2 contributes to (hem)immunoreceptor tyrosine-based activation motif-mediated signaling in platelets.Circulation research · 2014Article
- Fucoidan is a novel platelet agonist for the C-type lectin-like receptor 2 (CLEC-2).The Journal of biological chemistry · 2013Article
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe adapter proteins SLP-76 and LAT have been shown to play critical roles in the activation of PLCgamma2 in platelets downstream of GPVI/FcRgamma and the C-type lectin receptor CLEC-2. SLP-76 is constitutively associated with the adapter Gads in platelets, which also binds to tyrosine phosphorylated LAT, thereby providing a potential pathway of regulation of SLP-76.
objectiveIn the present study, we have compared the role of Gads alongside that of LAT following activation of the major platelet glycoprotein receptors using mice deficient in the two adapter proteins.
resultsGads was found to be required for the efficient onset of aggregation and secretion in response to submaximal stimulation of GPVI and CLEC-2, but to be dispensable for activation following stronger stimulation of the two receptors. Gads was also dispensable for spreading induced through integrin alpha(IIb)beta(3) or the GPIb-IX-V complex. Further, Gads plays a negligible role in aggregate formation on collagen at an arteriolar rate of shear. In stark contrast, platelets deficient in the adapter LAT exhibit a marked decrease in aggregation and secretion following activation of GPVI and CLEC-2, and are unable to form stable aggregates on collagen at arteriolar shear.
conclusionsThe results demonstrate that Gads plays a key role in linking the adapter LAT to SLP-76 in response to weak activation of GPVI and CLEC-2 whereas LAT is required for full activation over a wider range of agonist concentrations. These results reveal the presence of a Gads-independent pathway of platelet activation downstream of LAT.
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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.