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Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets

Retinoid X receptors (RXRs) are important transcriptional nuclear hormone receptors, acting as either homodimers or the binding partner for at least one fourth of all the known human nuclear receptors. Functional nongenomic effects of nuclear receptors are poorly understood; however, recently peroxi...

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Autores principales: Moraes, Leonardo A., Swales, Karen E., Wray, Jessica A., Damazo, Amilcar, Gibbins, Jonathan M., Warner, Timothy D., Bishop-Bailey, David
Formato: Texto
Lenguaje:English
Publicado: American Society of Hematology 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612640/
https://www.ncbi.nlm.nih.gov/pubmed/17213293
http://dx.doi.org/10.1182/blood-2006-05-022566
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author Moraes, Leonardo A.
Swales, Karen E.
Wray, Jessica A.
Damazo, Amilcar
Gibbins, Jonathan M.
Warner, Timothy D.
Bishop-Bailey, David
author_facet Moraes, Leonardo A.
Swales, Karen E.
Wray, Jessica A.
Damazo, Amilcar
Gibbins, Jonathan M.
Warner, Timothy D.
Bishop-Bailey, David
author_sort Moraes, Leonardo A.
collection PubMed
description Retinoid X receptors (RXRs) are important transcriptional nuclear hormone receptors, acting as either homodimers or the binding partner for at least one fourth of all the known human nuclear receptors. Functional nongenomic effects of nuclear receptors are poorly understood; however, recently peroxisome proliferator-activated receptor (PPAR) γ, PPARβ, and the glucocorticoid receptor have all been found active in human platelets. Human platelets express RXRα and RXRβ. RXR ligands inhibit platelet aggregation and TXA(2) release to ADP and the TXA(2) receptors, but only weakly to collagen. ADP and TXA(2) both signal via the G protein, Gq. RXR rapidly binds Gq but not Gi/z/o/t/gust in a ligand-dependent manner and inhibits Gq-induced Rac activation and intracellular calcium release. We propose that RXR ligands may have beneficial clinical actions through inhibition of platelet activation. Furthermore, our results demonstrate a novel nongenomic mode for nuclear receptor action and a functional cross-talk between G-protein and nuclear receptor signaling families.
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spelling pubmed-26126402009-01-23 Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets Moraes, Leonardo A. Swales, Karen E. Wray, Jessica A. Damazo, Amilcar Gibbins, Jonathan M. Warner, Timothy D. Bishop-Bailey, David Blood Hemostasis, Thrombosis, and Vascular Biology Retinoid X receptors (RXRs) are important transcriptional nuclear hormone receptors, acting as either homodimers or the binding partner for at least one fourth of all the known human nuclear receptors. Functional nongenomic effects of nuclear receptors are poorly understood; however, recently peroxisome proliferator-activated receptor (PPAR) γ, PPARβ, and the glucocorticoid receptor have all been found active in human platelets. Human platelets express RXRα and RXRβ. RXR ligands inhibit platelet aggregation and TXA(2) release to ADP and the TXA(2) receptors, but only weakly to collagen. ADP and TXA(2) both signal via the G protein, Gq. RXR rapidly binds Gq but not Gi/z/o/t/gust in a ligand-dependent manner and inhibits Gq-induced Rac activation and intracellular calcium release. We propose that RXR ligands may have beneficial clinical actions through inhibition of platelet activation. Furthermore, our results demonstrate a novel nongenomic mode for nuclear receptor action and a functional cross-talk between G-protein and nuclear receptor signaling families. American Society of Hematology 2007-05-01 /pmc/articles/PMC2612640/ /pubmed/17213293 http://dx.doi.org/10.1182/blood-2006-05-022566 Text en © 2007 by The American Society of Hematology This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/us/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Hemostasis, Thrombosis, and Vascular Biology
Moraes, Leonardo A.
Swales, Karen E.
Wray, Jessica A.
Damazo, Amilcar
Gibbins, Jonathan M.
Warner, Timothy D.
Bishop-Bailey, David
Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets
title Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets
title_full Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets
title_fullStr Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets
title_full_unstemmed Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets
title_short Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets
title_sort nongenomic signaling of the retinoid x receptor through binding and inhibiting gq in human platelets
topic Hemostasis, Thrombosis, and Vascular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612640/
https://www.ncbi.nlm.nih.gov/pubmed/17213293
http://dx.doi.org/10.1182/blood-2006-05-022566
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