ArticleThe Journal of biological chemistry2010
Thrombin and collagen induce a feedback inhibitory signaling pathway in platelets involving dissociation of the catalytic subunit of protein kinase A from an NFkappaB-IkappaB complex.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 149 citations in OpenAlex.
- Molecular-level understanding of the aging bone and regeneration mechanisms using computational methods.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Review
- Protease-Activated Receptor 1 as an Endogenous Model of Peptidergic Gαq-Gα12-Biased G Protein Signaling.bioRxiv : the preprint server for biology · 2026Article
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- Protease-activated receptor 1 as an endogenous model of peptidergic Gαq-Gα12-biased G protein signaling.Frontiers in molecular biosciences · 2026Article
- Abnormal activation of platelets and inflammation in smoking-induced rheumatoid arthritis is alleviated by 3,3'-diindolylmethane.Genes and immunity · 2025Article
- Article
- Light induces a rapid increase in cAMP and activates PKA in rod outer segments of the frog retina.The Journal of general physiology · 2024Article
- Antiplatelet Effects of Flavonoid Aglycones Are Mediated by Activation of Cyclic Nucleotide-Dependent Protein Kinases.International journal of molecular sciences · 2024Article
- Non-canonical non-genomic morphogen signaling in anucleate platelets: a critical determinant of prothrombotic function in circulation.Cell communication and signaling : CCS · 2024Review
- Changes in the Proteome of Platelets from Patients with Critical Progression of COVID-19.Cells · 2023Article
- Genetic associations between miR‑200bT>C and miR‑495A>C polymorphisms and hypertension susceptibility.Experimental and therapeutic medicine · 2023Article
- Effects of the interactions between platelets with other cells in tumor growth and progression.Frontiers in immunology · 2023Review
- Activation of Most Toll-Like Receptors in Whole Human Blood Attenuates Platelet Deposition on Collagen under Flow.Journal of immunology research · 2023Article
- Review
- Topical Wound Treatment with a Nitric Oxide-Releasing PDE5 Inhibitor Formulation Enhances Blood Perfusion and Promotes Healing in Mice.Pharmaceutics · 2022Article
- Platelet Hemostasis Reactions at Different Temperatures Correlate with Intracellular Calcium Concentration.International journal of molecular sciences · 2022Article
- ML355 Modulates Platelet Activation and Prevents ABT-737 Induced Apoptosis in Platelets.The Journal of pharmacology and experimental therapeutics · 2022Article
- Article
- Nitrous anhydrase activity of carbonic anhydrase II: cysteine is required for nitric oxide (NO) dependent phosphorylation of VASP in human platelets.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Imaging of Intracellular and Plasma Membrane Pools of PI(4,5)PLife (Basel, Switzerland) · 2021Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein kinase A (PKA) activation by cAMP phosphorylates multiple target proteins in numerous platelet inhibitory pathways that have a very important role in maintaining circulating platelets in a resting state. Here we show that in thrombin- and collagen-stimulated platelets, PKA is activated by cAMP-independent mechanisms involving dissociation of the catalytic subunit of PKA (PKAc) from an NFkappaB-IkappaBalpha-PKAc complex. We demonstrate mRNA and protein expression for most of the NFkappaB family members in platelets. From resting platelets, PKAc was co-immunoprecipitated with IkappaBalpha, and conversely, IkappaBalpha was also co-immunoprecipitated with PKAc. This interaction was significantly reduced in thrombin- and collagen-stimulated platelets. Stimulation of platelets with thrombin- or collagen-activated IKK, at least partly by PI3 kinase-dependent pathways, leading to phosphorylation of IkappaBalpha, disruption of an IkappaBalpha-PKAc complex, and release of free, active PKAc, which phosphorylated VASP and other PKA substrates. IKK inhibitor inhibited thrombin-stimulated IkBalpha phosphorylation, PKA-IkBalpha dissociation, and VASP phosphorylation, and potentiated integrin alphaIIbbeta3 activation and the early phase of platelet aggregation. We conclude that thrombin and collagen not only cause platelet activation but also appear to fine-tune this response by initiating downstream NFkappaB-dependent PKAc activation, as a novel feedback inhibitory signaling mechanism for preventing undesired platelet activation.
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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.