دورية أكاديمية
Finding the "switch" in platelet activation: prediction of key mediators involved in reversal of platelet activation using a novel network biology approach.
| العنوان: | Finding the "switch" in platelet activation: prediction of key mediators involved in reversal of platelet activation using a novel network biology approach. |
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| المؤلفون: | Lemmens TP; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands., Coenen DM; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands., Swieringa F; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands., Niessen ICL; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands., Coort SLM; Department of Bioinformatics -BiGCaT, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands., Koenen RR; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands., Kutmon M; Department of Bioinformatics -BiGCaT, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands; Maastricht Centre for Systems Biology (MaCSBio), Maastricht University, Maastricht, the Netherlands., Cosemans JMEM; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands. Electronic address: judith.cosemans@maastrichtuniversity.nl. |
| المصدر: | Journal of proteomics [J Proteomics] 2022 Jun 15; Vol. 261, pp. 104577. Date of Electronic Publication: 2022 Mar 26. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101475056 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1876-7737 (Electronic) Linking ISSN: 18743919 NLM ISO Abbreviation: J Proteomics Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam : Elsevier |
| مواضيع طبية MeSH: | Cyclic AMP*/metabolism , Platelet Activation*/physiology, Blood Platelets/metabolism ; Phosphorylation ; Proteomics |
| مستخلص: | The cAMP-protein kinase A (PKA) pathway in platelets is important for both platelet activation and inactivation. We hypothesize that proteins/processes downstream of the cAMP-PKA pathway that are regulated after platelet activation ánd subsequent inactivation can serve as a "switch" in platelet activation and inhibition. We used a STRING-based protein-protein interaction network from proteins of interest distilled from publicly available quantitative platelet proteome datasets. The protein network was integrated with biological pathway information by functional enrichment analysis, phosphorylation by PKA, and drug-target information. Functional enrichment analysis revealed biological processes related to vesicle secretion and cytoskeletal reorganization to be overrepresented among these 30 proteins coinciding with topological clusters in the network. Our method identified proteins/processes with functions related to vesicle transport, cyclin-dependent protein kinases, tight junctions, and small GTPases as potential switches in platelet activation and inhibition. Next to established enzymes in cAMP-PKA signaling, such as PDE3A, proteins with an unknown/less well-known role in platelet biology, such as Stonin-2 and ABLIM-3, emerged from our analysis as interesting candidates for reversal of platelet activation. Our method can be used to repurpose existing datasets and provide a coherent overview of mechanisms involved to predict novel connections, by visually integrating multiple datasets. SIGNIFICANCE: This article presents a novel approach of visually incorporating multiple existing tools and proteomics datasets and in doing so provides novel insight into the complex molecular mechanisms involved in platelet activation. Using our approach, we also highlight several interesting candidates for future research into pathologies with high platelet reactivity. (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Data integration and visualization; Platelet activation and inhibition; Platelet reactivity; Platelet switch |
| المشرفين على المادة: | E0399OZS9N (Cyclic AMP) |
| تواريخ الأحداث: | Date Created: 20220330 Date Completed: 20220512 Latest Revision: 20220529 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.jprot.2022.104577 |
| PMID: | 35351662 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1876-7737 |
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| DOI: | 10.1016/j.jprot.2022.104577 |