ArticleBlood2006
Sequential activation of p38 and ERK pathways by cGMP-dependent protein kinase leading to activation of the platelet integrin alphaIIb beta3.
Article in Blood, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 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.
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Who cites it
66 citing papers in PubMed, 151 citations in OpenAlex.
- Ferulic acid in combination with ginsenoside Rb1 alleviates myocardial no-reflow by inhibiting platelet HMGB1 release and NET formation.Chinese medicine · 2026Article
- Chrysoeriol Exerts Antiplatelet Effects by Regulating cAMP/cGMP and PI3K/MAPK Pathway.Biomolecules & therapeutics · 2026Article
- The Involvement of PI3K-Akt Signaling in the Clinical and Pathological Findings of Idiopathic Multicentric Castleman Disease-Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis, and Organomegaly and Not Otherwise Specified Subtypes.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2025Article
- Isoform-specific optical activation of kinase function reveals p38-ERK signaling crosstalk.RSC chemical biology · 2023Article
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- Signaling mechanisms of the platelet glycoprotein Ib-IX complex.Platelets · 2022Review
- Unfolded Protein Response Differentially Modulates the Platelet Phenotype.Circulation research · 2022Article
- Comprehensive overview of COVID-19-related respiratory failure: focus on cellular interactions.Cellular & molecular biology letters · 2022Review
- Platelet dysfunction in platelet-type von Willebrand disease due to the constitutive triggering of the Lyn-PECAM1 inhibitory pathway.Haematologica · 2022Article
- HIV and FIV glycoproteins increase cellular tau pathology via cGMP-dependent kinase II activation.Journal of cell science · 2022Article
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- The GPIbα intracellular tail - role in transducing VWF- and collagen/GPVI-mediated signaling.Haematologica · 2022Article
- Analysis of mRNA and protein kidney injury Molecule-1 (KIM-1) expression in a kidney model during the initiation phase of ischemia reperfusion injury.Annals of medicine and surgery (2012) · 2022Article
- Signal transduction pathway involved in platelet activation in immune thrombotic thrombocytopenia after COVID-19 vaccination.Haematologica · 2022Article
- Effect of Evodiamine on Collagen-Induced Platelet Activation and Thrombosis.BioMed research international · 2022Article
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- Differential regulation of the platelet GPIb-IX complex by anti-GPIbβ antibodies.Journal of thrombosis and haemostasis : JTH · 2021Article
- Is Antiplatelet Therapy Contraindicated After Platelet-Rich Plasma Treatment? A Narrative Review.Orthopaedic journal of sports medicine · 2021Review
- Influence of integrins on thrombus formation: a road leading to the unravelling of DVT.Molecular and cellular biochemistry · 2021Review
6 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
5 authors at 1 institution in 1 country.
Funding
Abstract
Integrin activation (inside-out signaling) in platelets can be initiated by agonists such as von Willebrand factor (VWF) and thrombin. Here we show that a mitogen-activated protein kinase (MAPK), p38, plays an important role in the activation of integrin alphaIIb beta3 induced by VWF and thrombin. A dominant-negative mutant of p38, p38AF, inhibits alphaIIb beta3 activation induced by VWF binding to its receptor, the platelet glycoprotein Ib-IX (GPIb-IX), and p38 inhibitors diminish platelet aggregation induced by VWF or low-dose thrombin. The inhibitory effect of p38 inhibitor is unlikely to be caused by the previous suggested effect on cyclo-oxygenase, as inhibition also was observed in the presence of high concentrations of cyclo-oxygenase inhibitor, aspirin. VWF or thrombin induces p38 activation, which is inhibited in cGMP-dependent protein kinase (PKG)-knockout mouse platelets and PKG inhibitor-treated human platelets, indicating that activation of p38 is downstream from PKG in the signaling pathway. p38AF or p38 inhibitors diminish PKG-induced phosphorylation of extracellular stimuli-responsive kinase (ERK), which also is important in integrin activation. Thus, p38 plays an important role in mediating PKG-dependent activation of ERK. These data delineate a novel signaling pathway in which platelet agonists sequentially activate PKG, p38, and ERK pathways leading to integrin activation.
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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.