ArticleThe Journal of biological chemistry2011
Distinct roles for Rap1b protein in platelet secretion and integrin αIIbβ3 outside-in signaling.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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
45 citing papers in PubMed, 66 citations in OpenAlex.
- Human CalDAG-GEFI gene (RASGRP2) mutation affects platelet function and causes severe bleeding.The Journal of experimental medicine · 2014Trial
- Outside-In Signaling as a Detonator-like Stimulus of Integrin Activation by Promoting Both Affinity and Avidity.Biomolecules · 2026Review
- A novel G13-RAPGEF2-RAP1 signaling pathway critical for platelet adhesion and aggregation.Blood · 2026Article
- Platelet gene signatures detecting pulmonary artery stenosis in patients with pulmonary hypertension.Orphanet journal of rare diseases · 2026Article
- Thiol isomerase ERp18 enhances platelet activation and arterial thrombosis.Research and practice in thrombosis and haemostasis · 2025Article
- Review
- Roles of G proteins and their GTPase-activating proteins in platelets.Bioscience reports · 2024Review
- Platelet C3G: a key player in vesicle exocytosis, spreading and clot retraction.Cellular and molecular life sciences : CMLS · 2024Article
- Altered Cortical Palmitoylation Induces Widespread Molecular Disturbances in Parkinson's Disease.International journal of molecular sciences · 2022Article
- Reversible Platelet Integrin αIIbβ3 Activation and Thrombus Instability.International journal of molecular sciences · 2022Review
- Platelets inhibit development of atherosclerosis in atherosclerotic mice.Cell cycle (Georgetown, Tex.) · 2022Article
- Roxadustat Does Not Affect Platelet Production, Activation, and Thrombosis Formation.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Article
- C3G contributes to platelet activation and aggregation by regulating major signaling pathways.Signal transduction and targeted therapy · 2020Article
- Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- MiR-181a Reduces Platelet ActivationMicroRNA (Shariqah, United Arab Emirates) · 2020Article
- Critical roles for the phosphatidylinositide 3-kinase isoforms p110β and p110γ in thrombopoietin-mediated priming of platelet function.Scientific reports · 2019Article
- Small GTPases in platelet membrane trafficking.Platelets · 2019Review
- RAP GTPases and platelet integrin signaling.Platelets · 2019Review
- Direct Rap1/Talin1 interaction regulates platelet and neutrophil integrin activity in mice.Blood · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Rap1b is activated by platelet agonists and plays a critical role in integrin α(IIb)β(3) inside-out signaling and platelet aggregation. Here we show that agonist-induced Rap1b activation plays an important role in stimulating secretion of platelet granules. We also show that α(IIb)β(3) outside-in signaling can activate Rap1b, and integrin outside-in signaling-mediated Rap1b activation is important in facilitating platelet spreading on fibrinogen and clot retraction. Rap1b-deficient platelets had diminished ATP secretion and P-selectin expression induced by thrombin or collagen. Importantly, addition of low doses of ADP and/or fibrinogen restored aggregation of Rap1b-deficient platelets. Furthermore, we found that Rap1b was activated by platelet spreading on immobilized fibrinogen, a process that was not affected by P2Y(12) or TXA(2) receptor deficiency, but was inhibited by the selective Src inhibitor PP2, the PKC inhibitor Ro-31-8220, or the calcium chelator demethyl-1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis. Clot retraction was abolished, and platelet spreading on fibrinogen was diminished in Rap1b-deficient platelets compared with wild-type controls. The defects in clot retraction and spreading on fibrinogen of Rap1b-deficient platelets were not rescued by addition of MnCl(2), which elicits α(IIb)β(3) outside-in signaling in the absence of inside-out signaling. Thus, our results reveal two different activation mechanisms of Rap1b as well as novel functions of Rap1b in platelet secretion and in integrin α(IIb)β(3) outside-in signaling.
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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.