ArticleSignal transduction and targeted therapy2020
C3G contributes to platelet activation and aggregation by regulating major signaling pathways.
Article in Signal transduction and targeted therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Systemic metabolic dysfunction drives platelet-mediated inflammation, fibrogenesis, and hepatocarcinogenesis in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- A novel G13-RAPGEF2-RAP1 signaling pathway critical for platelet adhesion and aggregation.Blood · 2026Article
- Nintedanib Eye Drops Inhibit Alkali Burn-Induced Corneal Neovascularization Via RAP1/MEK/ERK Signaling Pathway.Investigative ophthalmology & visual science · 2026Article
- C3G deregulation uncovers a dual role in B-cell lymphoma: tumor suppression and enhanced metastasis via Rap1 and Rac2 signaling.Cell communication and signaling : CCS · 2025Article
- Identification of salvianolic acid A as an ADP receptor-selective and Gq/IPChinese medicine · 2025Article
- Acute histopathological and biochemical changes in saphenous vein grafts during coronary artery bypass grafting: A closer look at mTOR signaling.Turk gogus kalp damar cerrahisi dergisi · 2025Article
- Research progress of CD73-adenosine signaling regulating hepatocellular carcinoma through tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2025Review
- Examining the Effects of the RUNX1 p.Leu43Ser Variant on FPD/AML Phenotypes Using a CRISPR/Cas9-Generated Knock-In Murine Model.Biomolecules · 2025Article
- C3G promotes bone marrow adipocyte expansion and hematopoietic regeneration after myeloablation by enhancing megakaryocyte niche function.Journal of hematology & oncology · 2025Article
- Platelet C3G protects from liver fibrosis, while enhancing tumor growth through regulation of the immune response.The Journal of pathology · 2025Article
- Targeting Rap1b signaling cascades with CDNF: Mitigating platelet activation, plasma oxylipins and reperfusion injury in stroke.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Review
- Combined HRAS and NRAS ablation induces a RASopathy phenotype in mice.Cell communication and signaling : CCS · 2024Article
- Platelet C3G: a key player in vesicle exocytosis, spreading and clot retraction.Cellular and molecular life sciences : CMLS · 2024Article
- PKCα Induced the Generation of Extracellular Vesicles in Activated Platelets to Promote Breast Cancer Metastasis.International journal of biological sciences · 2024Article
- New and Old Key Players in Liver Cancer.International journal of molecular sciences · 2023Review
- Review
- Distinct bidirectional regulation of LFA1 and α4β7 by Rap1 and integrin adaptors in T cells under shear flow.Cell reports · 2023Article
- Review
- Differential Regulation of GPVI-Induced Btk and Syk Activation by PKC, PKA and PP2A in Human Platelets.International journal of molecular sciences · 2023Article
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Authors and funding
10 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
C3G is a GEF (guanine nucleotide exchange factor) for Rap GTPases, among which the isoform Rap1b is an essential protein in platelet biology. Using transgenic mouse models with platelet-specific overexpression of C3G or mutant C3GΔCat, we have unveiled a new function of C3G in regulating the hemostatic function of platelets through its participation in the thrombin-PKC-Rap1b pathway. C3G also plays important roles in angiogenesis, tumor growth, and metastasis through its regulation of the platelet secretome. In addition, C3G contributes to megakaryopoiesis and thrombopoiesis. Here, we used a platelet-specific C3G-KO mouse model to further support the role of C3G in hemostasis. C3G-KO platelets showed a significant delay in platelet activation and aggregation as a consequence of the defective activation of Rap1, which resulted in decreased thrombus formation in vivo. Additionally, we explored the contribution of C3G-Rap1b to platelet signaling pathways triggered by thrombin, PMA or ADP, in the referenced transgenic mouse model, through the use of a battery of specific inhibitors. We found that platelet C3G is phosphorylated at Tyr504 by a mechanism involving PKC-Src. This phosphorylation was shown to be positively regulated by ERKs through their inhibition of the tyrosine phosphatase Shp2. Moreover, C3G participates in the ADP-P2Y12-PI3K-Rap1b pathway and is a mediator of thrombin-TXA
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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.