ArticleThe Journal of clinical investigation2015
RASA3 is a critical inhibitor of RAP1-dependent platelet activation.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 135 citations in OpenAlex.
- Trial
- RAS P21 Protein Activator 3 finetunes Type I immunity by limiting HCK-mediated STAT4 phosphorylation.Nature communications · 2026Article
- Temporal phosphoproteomics reveals key regulators of procoagulant COAT platelet generation.Blood vessels, thrombosis & hemostasis · 2026Article
- A novel G13-RAPGEF2-RAP1 signaling pathway critical for platelet adhesion and aggregation.Blood · 2026Article
- A Rasa3-Gαi signaling axis orchestrates B lymphocyte trafficking into and through lymphoid organs.Cell reports · 2026Article
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- Can drug-induced platelet dysfunction be reversed?Research and practice in thrombosis and haemostasis · 2026Review
- Review
- Modeling platelet P2YBiophysical journal · 2025Article
- Disrupted priming within draining lymph nodes drives immune quiescence in gastric cancer.bioRxiv : the preprint server for biology · 2025Article
- Roles of G proteins and their GTPase-activating proteins in platelets.Bioscience reports · 2024Review
- Exploring bias in platelet P2YBritish journal of pharmacology · 2024Review
- Inositol 1,3,4,5-tetrakisphosphate: a remarkable second messenger in platelet signaling.Research and practice in thrombosis and haemostasis · 2024Article
- Evidence that inositol 1,4,5-trisphosphate 3-kinase and inositol 1,3,4,5-tetrakisphosphate are negative regulators of platelet function.Research and practice in thrombosis and haemostasis · 2024Article
- LA-GEM: imputation of gene expression with incorporation of Local Ancestry.Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing · 2024Article
- The CalDAG-GEFI/Rap1/αIIbβ3 axis minimally contributes to accelerated platelet clearance in mice with constitutive store-operated calcium entry.Platelets · 2023Article
- Mind the GAP: RASA2 and RASA3 GTPase-activating proteins as gatekeepers of T cell activation and adhesion.Trends in immunology · 2023Review
- Article
- Loss of P2YJournal of thrombosis and haemostasis : JTH · 2023Article
- Distinct bidirectional regulation of LFA1 and α4β7 by Rap1 and integrin adaptors in T cells under shear flow.Cell reports · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
The small GTPase RAP1 is critical for platelet activation and thrombus formation. RAP1 activity in platelets is controlled by the GEF CalDAG-GEFI and an unknown regulator that operates downstream of the adenosine diphosphate (ADP) receptor, P2Y12, a target of antithrombotic therapy. Here, we provide evidence that the GAP, RASA3, inhibits platelet activation and provides a link between P2Y12 and activation of the RAP1 signaling pathway. In mice, reduced expression of RASA3 led to premature platelet activation and markedly reduced the life span of circulating platelets. The increased platelet turnover and the resulting thrombocytopenia were reversed by concomitant deletion of the gene encoding CalDAG-GEFI. Rasa3 mutant platelets were hyperresponsive to agonist stimulation, both in vitro and in vivo. Moreover, activation of Rasa3 mutant platelets occurred independently of ADP feedback signaling and was insensitive to inhibitors of P2Y12 or PI3 kinase. Together, our results indicate that RASA3 ensures that circulating platelets remain quiescent by restraining CalDAG-GEFI/RAP1 signaling and suggest that P2Y12 signaling is required to inhibit RASA3 and enable sustained RAP1-dependent platelet activation and thrombus formation at sites of vascular injury. These findings provide insight into the antithrombotic effect of P2Y12 inhibitors and may lead to improved diagnosis and treatment of platelet-related disorders.
Indexed as
Identifiers
What OpenQuestion holds
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.