ArticleProceedings of the National Academy of Sciences of the United States of America1997
Platelet signal transduction defect with Galpha subunit dysfunction and diminished Galphaq in a patient with abnormal platelet responses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 97 citations in OpenAlex.
- A regulatory node involving GαJournal of thrombosis and haemostasis : JTH · 2023Article
- Strengths and Weaknesses of Light Transmission Aggregometry in Diagnosing Hereditary Platelet Function Disorders.Journal of clinical medicine · 2020Review
- Receptor-interacting protein kinase 3 promotes platelet activation and thrombosis.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Protease-activated receptor 4: from structure to function and back again.British journal of pharmacology · 2016Review
- Protease-activated receptor (PAR) 1 and PAR4 differentially regulate factor V expression from human platelets.Molecular pharmacology · 2013Article
- Targeting protease-activated receptor-1 with cell-penetrating pepducins in lung cancer.The American journal of pathology · 2011Article
- Article
- RhoA downstream of G(q) and G(12/13) pathways regulates protease-activated receptor-mediated dense granule release in platelets.Biochemical pharmacology · 2009Article
- Phorbol 12-myristate 13-acetate (PMA) responsive sequence in Galphaq promoter during megakaryocytic differentiation. Regulation by EGR-1 and MAP kinase pathway.Thrombosis and haemostasis · 2008Article
- Article
- A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets.The Journal of experimental medicine · 2007Article
- Biological properties of a specific Galpha q/11 inhibitor, YM-254890, on platelet functions and thrombus formation under high-shear stress.British journal of pharmacology · 2006Article
- Protease activated receptors in cardiovascular function and disease.Molecular and cellular biochemistry · 2004Article
- Protein kinase C- and calcium-regulated pathways independently synergize with Gi pathways in agonist-induced fibrinogen receptor activation.The Biochemical journal · 2002Article
- Coactivation of two different G protein-coupled receptors is essential for ADP-induced platelet aggregation.Proceedings of the National Academy of Sciences of the United States of America · 1998Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
G proteins play a major role in signal transduction upon platelet activation. We have previously reported a patient with impaired agonist-induced aggregation, secretion, arachidonate release, and Ca2+ mobilization. Present studies demonstrated that platelet phospholipase A2 (cytosolic and membrane) activity in the patient was normal. Receptor-mediated activation of glycoprotein (GP) IIb-IIIa complex measured by flow cytometry using antibody PAC-1 was diminished despite normal amounts of GPIIb-IIIa on platelets. Ca2+ release induced by guanosine 5'-[gamma-thio]triphosphate (GTP[gammaS]) was diminished in the patient's platelets, suggesting a defect distal to agonist receptors. GTPase activity (a function of alpha-subunit) in platelet membranes was normal in resting state but was diminished compared with normal subjects on stimulation with thrombin, platelet-activating factor, or the thromboxane A2 analog U46619. Binding of 35S-labeled GTP[gammaS] to platelet membranes was decreased under both basal and thrombin-stimulated states. Iloprost (a stable prostaglandin I2 analog) -induced rise in cAMP (mediated by Galphas) and its inhibition (mediated by Galphai) by thrombin in the patient's platelet membranes were normal. Immunoblot analysis of Galpha subunits in the patient's platelet membranes showed a decrease in Galphaq (<50%) but not Galphai, Galphaz, Galpha12, and Galpha13. These studies provide evidence for a hitherto undescribed defect in human platelet G-protein alpha-subunit function leading to impaired platelet responses, and they provide further evidence for a major role of Galphaq in thrombin-induced responses.
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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.