ArticleBlood2008
CalDAG-GEFI and protein kinase C represent alternative pathways leading to activation of integrin alphaIIbbeta3 in platelets.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
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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.
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Who cites it
69 citing papers in PubMed, 129 citations in OpenAlex.
- Human CalDAG-GEFI gene (RASGRP2) mutation affects platelet function and causes severe bleeding.The Journal of experimental medicine · 2014Trial
- A novel G13-RAPGEF2-RAP1 signaling pathway critical for platelet adhesion and aggregation.Blood · 2026Article
- Glycoprotein Ibα-Dependent Platelet Activation is Essential for Tumor Cell-Platelet Interaction and Experimental Metastasis.MedComm · 2025Article
- Platelet C3G: a key player in vesicle exocytosis, spreading and clot retraction.Cellular and molecular life sciences : CMLS · 2024Article
- High-throughput microfluidic blood testing to phenotype genetically linked platelet disorders: an aid to diagnosis.Blood advances · 2023Article
- Protease-activated receptors and glycoprotein VI cooperatively drive the platelet component in thromboelastography.Journal of thrombosis and haemostasis : JTH · 2023Article
- The relative importance of platelet integrins in hemostasis, thrombosis and beyond.Haematologica · 2023Review
- Reversible Platelet Integrin αIIbβ3 Activation and Thrombus Instability.International journal of molecular sciences · 2022Review
- Platelet dysfunction in platelet-type von Willebrand disease due to the constitutive triggering of the Lyn-PECAM1 inhibitory pathway.Haematologica · 2022Article
- Structural, biochemical, and functional properties of the Rap1-Interacting Adaptor Molecule (RIAM).Biomedical journal · 2022Review
- CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant inInternational journal of molecular sciences · 2021Article
- The Role of RASGRP2 in Vascular Endothelial Cells-A Mini Review.International journal of molecular sciences · 2021Review
- CRISPR-edited megakaryocytes for rapid screening of platelet gene functions.Blood advances · 2021Article
- Lipid Receptor GPR31 (G-Protein-Coupled Receptor 31) Regulates Platelet Reactivity and Thrombosis Without Affecting Hemostasis.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Platelet transfusion for patients with platelet dysfunction: effectiveness, mechanisms, and unanswered questions.Current opinion in hematology · 2020Review
- Strengths and Weaknesses of Light Transmission Aggregometry in Diagnosing Hereditary Platelet Function Disorders.Journal of clinical medicine · 2020Review
- Subcellular localization of Rap1 GTPase activator CalDAG-GEFI is orchestrated by interaction of its atypical C1 domain with membrane phosphoinositides.Journal of thrombosis and haemostasis : JTH · 2020Article
- RasGRP2 Structure, Function and Genetic Variants in Platelet Pathophysiology.International journal of molecular sciences · 2020Review
- Impaired hemostatic activity of healthy transfused platelets in inherited and acquired platelet disorders: Mechanisms and implications.Science translational medicine · 2019Article
- Ether lipid metabolism by AADACL1 regulates platelet function and thrombosis.Blood advances · 2019Article
9 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
Second messenger-mediated inside-out activation of integrin alphaIIbbeta3 is a key step in platelet aggregation. We recently showed strongly impaired but not absent alphaIIbbeta3-mediated aggregation of CalDAG-GEFI-deficient platelets activated with various agonists. Here we further evaluated the roles of CalDAG-GEFI and protein kinase C (PKC) for alphaIIbbeta3 activation in platelets activated with a PAR4 receptor-specific agonist, GYPGKF (PAR4p). Compared with wild-type controls, platelets treated with the PKC inhibitor Ro31-8220 or CalDAG-GEFI-deficient platelets showed a marked defect in aggregation at low (< 1mM PAR4p) but not high PAR4p concentrations. Blocking of PKC function in CalDAG-GEFI-deficient platelets, how-ever, strongly decreased aggregation at all PAR4p concentrations, demonstrating that CalDAG-GEFI and PKC represent separate, but synergizing, pathways important for alphaIIbbeta3 activation. PAR4p-induced aggregation in the absence of CalDAG-GEFI required cosignaling through the Galphai-coupled receptor for ADP, P2Y12. Independent roles for CalDAG-GEFI and PKC/Galphai signaling were also observed for PAR4p-induced activation of the small GTPase Rap1, with CalDAG-GEFI mediating the rapid but reversible activation of this small GTPase. In summary, our study identifies CalDAG-GEFI and PKC as independent pathways leading to Rap1 and alphaIIbbeta3 activation in mouse platelets activated through the PAR4 receptor.
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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.