Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6

Abstract Cyclooxygenase-2 catalyses the biosynthesis of prostaglandins from arachidonic acid but also the biosynthesis of prostaglandin glycerol esters (PG-Gs) from 2-arachidonoylglycerol. Previous studies identified PG-Gs as signalling molecules involved in inflammation. Thus, the glyceryl ester of...

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Autores principales:	Antje Brüser, Anne Zimmermann, Brenda C. Crews, Gregory Sliwoski, Jens Meiler, Gabriele M. König, Evi Kostenis, Vera Lede, Lawrence J. Marnett, Torsten Schöneberg
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0c6b5a4f249e46d79caac5439349ac48
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spelling	oai:doaj.org-article:0c6b5a4f249e46d79caac5439349ac482021-12-02T16:06:19ZProstaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y610.1038/s41598-017-02414-82045-2322https://doaj.org/article/0c6b5a4f249e46d79caac5439349ac482017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02414-8https://doaj.org/toc/2045-2322Abstract Cyclooxygenase-2 catalyses the biosynthesis of prostaglandins from arachidonic acid but also the biosynthesis of prostaglandin glycerol esters (PG-Gs) from 2-arachidonoylglycerol. Previous studies identified PG-Gs as signalling molecules involved in inflammation. Thus, the glyceryl ester of prostaglandin E2, PGE2-G, mobilizes Ca2+ and activates protein kinase C and ERK, suggesting the involvement of a G protein-coupled receptor (GPCR). To identify the endogenous receptor for PGE2-G, we performed a subtractive screening approach where mRNA from PGE2-G response-positive and -negative cell lines was subjected to transcriptome-wide RNA sequencing analysis. We found several GPCRs that are only expressed in the PGE2-G responder cell lines. Using a set of functional readouts in heterologous and endogenous expression systems, we identified the UDP receptor P2Y6 as the specific target of PGE2-G. We show that PGE2-G and UDP are both agonists at P2Y6, but they activate the receptor with extremely different EC50 values of ~1 pM and ~50 nM, respectively. The identification of the PGE2-G/P2Y6 pair uncovers the signalling mode of PG-Gs as previously under-appreciated products of cyclooxygenase-2.Antje BrüserAnne ZimmermannBrenda C. CrewsGregory SliwoskiJens MeilerGabriele M. KönigEvi KostenisVera LedeLawrence J. MarnettTorsten SchönebergNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Antje Brüser Anne Zimmermann Brenda C. Crews Gregory Sliwoski Jens Meiler Gabriele M. König Evi Kostenis Vera Lede Lawrence J. Marnett Torsten Schöneberg Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6
description	Abstract Cyclooxygenase-2 catalyses the biosynthesis of prostaglandins from arachidonic acid but also the biosynthesis of prostaglandin glycerol esters (PG-Gs) from 2-arachidonoylglycerol. Previous studies identified PG-Gs as signalling molecules involved in inflammation. Thus, the glyceryl ester of prostaglandin E2, PGE2-G, mobilizes Ca2+ and activates protein kinase C and ERK, suggesting the involvement of a G protein-coupled receptor (GPCR). To identify the endogenous receptor for PGE2-G, we performed a subtractive screening approach where mRNA from PGE2-G response-positive and -negative cell lines was subjected to transcriptome-wide RNA sequencing analysis. We found several GPCRs that are only expressed in the PGE2-G responder cell lines. Using a set of functional readouts in heterologous and endogenous expression systems, we identified the UDP receptor P2Y6 as the specific target of PGE2-G. We show that PGE2-G and UDP are both agonists at P2Y6, but they activate the receptor with extremely different EC50 values of ~1 pM and ~50 nM, respectively. The identification of the PGE2-G/P2Y6 pair uncovers the signalling mode of PG-Gs as previously under-appreciated products of cyclooxygenase-2.
format	article
author	Antje Brüser Anne Zimmermann Brenda C. Crews Gregory Sliwoski Jens Meiler Gabriele M. König Evi Kostenis Vera Lede Lawrence J. Marnett Torsten Schöneberg
author_facet	Antje Brüser Anne Zimmermann Brenda C. Crews Gregory Sliwoski Jens Meiler Gabriele M. König Evi Kostenis Vera Lede Lawrence J. Marnett Torsten Schöneberg
author_sort	Antje Brüser
title	Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6
title_short	Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6
title_full	Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6
title_fullStr	Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6
title_full_unstemmed	Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6
title_sort	prostaglandin e2 glyceryl ester is an endogenous agonist of the nucleotide receptor p2y6
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0c6b5a4f249e46d79caac5439349ac48
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_version_	1718385006092484608

Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6

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