ArticleAmerican journal of physiology. Cell physiology2018
Platelet procoagulant phenotype is modulated by a p38-MK2 axis that regulates RTN4/Nogo proximal to the endoplasmic reticulum: utility of pathway analysis.
Article in American journal of physiology. Cell physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Platelet Drp1 phosphorylation provides a platform for immune-based platelet function testing.Blood · 2026Article
- Hepatic kynurenic acid mediates phosphorylation of Nogo-A in the medial prefrontal cortex to regulate chronic stress-induced anxiety-like behaviors in mice.Acta pharmacologica Sinica · 2024Article
- Article
- Unfolded Protein Response Differentially Modulates the Platelet Phenotype.Circulation research · 2022Article
- Platelet proteome dynamics in hibernating 13-lined ground squirrels.Physiological genomics · 2021Article
- Platelet Proteomes, Pathways, and Phenotypes as Informants of Vascular Wellness and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- The Toll-Like Receptor 2 Ligand Pam2CSK4 Activates Platelet Nuclear Factor-κB and Bruton's Tyrosine Kinase Signaling to Promote Platelet-Endothelial Cell Interactions.Frontiers in immunology · 2021Article
- Article
- A Sample Preparation Protocol for High Throughput Immunofluorescence of Suspension Cells on an Adherent Surface.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Article
- Pathway Commons 2019 Update: integration, analysis and exploration of pathway data.Nucleic acids research · 2020Article
- Large-scale automated machine reading discovers new cancer-driving mechanisms.Database : the journal of biological databases and curation · 2018Article
- Rho GTPase regulation of reactive oxygen species generation and signalling in platelet function and disease.Small GTPasesReview
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Upon encountering physiological cues associated with damaged or inflamed endothelium, blood platelets set forth intracellular responses to ultimately support hemostatic plug formation and vascular repair. To gain insights into the molecular events underlying platelet function, we used a combination of interactome, pathway analysis, and other systems biology tools to analyze associations among proteins functionally modified by reversible phosphorylation upon platelet activation. While an interaction analysis mapped out a relative organization of intracellular mediators in platelet signaling, pathway analysis revealed directional signaling relations around protein kinase C (PKC) isoforms and mitogen-activated protein kinases (MAPKs) associated with platelet cytoskeletal dynamics, inflammatory responses, and hemostatic function. Pathway and causality analysis further suggested that platelets activate a specific p38-MK2 axis to phosphorylate RTN4 (reticulon-4, also known as Nogo), a Bcl-xl sequestration protein and critical regulator of endoplasmic reticulum (ER) physiology. In vitro, we find that platelets drive a p38-MK2-RTN4-Bcl-xl pathway associated with the regulation of the ER and platelet phosphatidylserine exposure. Together, our results support the use of pathway tools in the analysis of omics data sets as a means to help generate novel, mechanistic, and testable hypotheses for platelet studies while uncovering RTN4 as a putative regulator of platelet cell physiological responses.
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Registered trials
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