Sprouty2 and Spred1-2 proteins inhibit the activation of the ERK pathway elicited by cyclopentenone prostanoids.

Sprouty and Spred proteins have been widely implicated in the negative regulation of the fibroblast growth factor receptor-extracellular regulated kinase (ERK) pathway. In considering the functional role of these proteins, we explored their effects on ERK activation induced by cyclopentenone prostan...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Carlota A García-Domínguez, Natalia Martínez, Teresa Gragera, Andrea Pérez-Rodríguez, Diana Retana, Gonzalo León, Agustín Sánchez, José Luis Oliva, Dolores Pérez-Sala, José M Rojas
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/48e19c28ab1c458eae1f03da80e9dcd9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:48e19c28ab1c458eae1f03da80e9dcd9
record_format	dspace
spelling	oai:doaj.org-article:48e19c28ab1c458eae1f03da80e9dcd92021-11-18T06:58:26ZSprouty2 and Spred1-2 proteins inhibit the activation of the ERK pathway elicited by cyclopentenone prostanoids.1932-620310.1371/journal.pone.0016787https://doaj.org/article/48e19c28ab1c458eae1f03da80e9dcd92011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21364986/?tool=EBIhttps://doaj.org/toc/1932-6203Sprouty and Spred proteins have been widely implicated in the negative regulation of the fibroblast growth factor receptor-extracellular regulated kinase (ERK) pathway. In considering the functional role of these proteins, we explored their effects on ERK activation induced by cyclopentenone prostanoids, which bind to and activate Ras proteins. We therefore found that ectopic overexpression in HeLa cells of human Sprouty2, or human Spred1 or 2, inhibits ERK1/2 and Elk-1 activation triggered by the cyclopentenone prostanoids PGA(1) and 15d-PGJ(2). Furthermore, we found that in HT cells that do not express Sprouty2 due to hypermethylation of its gene-promoter, PGA(1)-provoked ERK activation was more intense and sustained compared to other hematopoietic cell lines with unaltered Sprouty2 expression. Cyclopentenone prostanoids did not induce Sprouty2 tyrosine phosphorylation, in agreement with its incapability to activate tyrosine-kinase receptors. However, Sprouty2 Y55F, which acts as a defective mutant upon tyrosine-kinase receptor stimulation, did not inhibit cyclopentenone prostanoids-elicited ERK pathway activation. In addition, Sprouty2 did not affect the Ras-GTP levels promoted by cyclopentenone prostanoids. These results unveil both common and differential features in the activation of Ras-dependent pathways by cyclopentenone prostanoids and growth factors. Moreover, they provide the first evidence that Sprouty and Spred proteins are negative regulators of the ERK/Elk-1 pathway activation induced not only by growth-factors, but also by reactive lipidic mediators.Carlota A García-DomínguezNatalia MartínezTeresa GrageraAndrea Pérez-RodríguezDiana RetanaGonzalo LeónAgustín SánchezJosé Luis OlivaDolores Pérez-SalaJosé M RojasPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e16787 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carlota A García-Domínguez Natalia Martínez Teresa Gragera Andrea Pérez-Rodríguez Diana Retana Gonzalo León Agustín Sánchez José Luis Oliva Dolores Pérez-Sala José M Rojas Sprouty2 and Spred1-2 proteins inhibit the activation of the ERK pathway elicited by cyclopentenone prostanoids.
description	Sprouty and Spred proteins have been widely implicated in the negative regulation of the fibroblast growth factor receptor-extracellular regulated kinase (ERK) pathway. In considering the functional role of these proteins, we explored their effects on ERK activation induced by cyclopentenone prostanoids, which bind to and activate Ras proteins. We therefore found that ectopic overexpression in HeLa cells of human Sprouty2, or human Spred1 or 2, inhibits ERK1/2 and Elk-1 activation triggered by the cyclopentenone prostanoids PGA(1) and 15d-PGJ(2). Furthermore, we found that in HT cells that do not express Sprouty2 due to hypermethylation of its gene-promoter, PGA(1)-provoked ERK activation was more intense and sustained compared to other hematopoietic cell lines with unaltered Sprouty2 expression. Cyclopentenone prostanoids did not induce Sprouty2 tyrosine phosphorylation, in agreement with its incapability to activate tyrosine-kinase receptors. However, Sprouty2 Y55F, which acts as a defective mutant upon tyrosine-kinase receptor stimulation, did not inhibit cyclopentenone prostanoids-elicited ERK pathway activation. In addition, Sprouty2 did not affect the Ras-GTP levels promoted by cyclopentenone prostanoids. These results unveil both common and differential features in the activation of Ras-dependent pathways by cyclopentenone prostanoids and growth factors. Moreover, they provide the first evidence that Sprouty and Spred proteins are negative regulators of the ERK/Elk-1 pathway activation induced not only by growth-factors, but also by reactive lipidic mediators.
format	article
author	Carlota A García-Domínguez Natalia Martínez Teresa Gragera Andrea Pérez-Rodríguez Diana Retana Gonzalo León Agustín Sánchez José Luis Oliva Dolores Pérez-Sala José M Rojas
author_facet	Carlota A García-Domínguez Natalia Martínez Teresa Gragera Andrea Pérez-Rodríguez Diana Retana Gonzalo León Agustín Sánchez José Luis Oliva Dolores Pérez-Sala José M Rojas
author_sort	Carlota A García-Domínguez
title	Sprouty2 and Spred1-2 proteins inhibit the activation of the ERK pathway elicited by cyclopentenone prostanoids.
title_short	Sprouty2 and Spred1-2 proteins inhibit the activation of the ERK pathway elicited by cyclopentenone prostanoids.
title_full	Sprouty2 and Spred1-2 proteins inhibit the activation of the ERK pathway elicited by cyclopentenone prostanoids.
title_fullStr	Sprouty2 and Spred1-2 proteins inhibit the activation of the ERK pathway elicited by cyclopentenone prostanoids.
title_full_unstemmed	Sprouty2 and Spred1-2 proteins inhibit the activation of the ERK pathway elicited by cyclopentenone prostanoids.
title_sort	sprouty2 and spred1-2 proteins inhibit the activation of the erk pathway elicited by cyclopentenone prostanoids.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/48e19c28ab1c458eae1f03da80e9dcd9
work_keys_str_mv	AT carlotaagarciadominguez sprouty2andspred12proteinsinhibittheactivationoftheerkpathwayelicitedbycyclopentenoneprostanoids AT nataliamartinez sprouty2andspred12proteinsinhibittheactivationoftheerkpathwayelicitedbycyclopentenoneprostanoids AT teresagragera sprouty2andspred12proteinsinhibittheactivationoftheerkpathwayelicitedbycyclopentenoneprostanoids AT andreaperezrodriguez sprouty2andspred12proteinsinhibittheactivationoftheerkpathwayelicitedbycyclopentenoneprostanoids AT dianaretana sprouty2andspred12proteinsinhibittheactivationoftheerkpathwayelicitedbycyclopentenoneprostanoids AT gonzaloleon sprouty2andspred12proteinsinhibittheactivationoftheerkpathwayelicitedbycyclopentenoneprostanoids AT agustinsanchez sprouty2andspred12proteinsinhibittheactivationoftheerkpathwayelicitedbycyclopentenoneprostanoids AT joseluisoliva sprouty2andspred12proteinsinhibittheactivationoftheerkpathwayelicitedbycyclopentenoneprostanoids AT doloresperezsala sprouty2andspred12proteinsinhibittheactivationoftheerkpathwayelicitedbycyclopentenoneprostanoids AT josemrojas sprouty2andspred12proteinsinhibittheactivationoftheerkpathwayelicitedbycyclopentenoneprostanoids
_version_	1718424099005399040

Sprouty2 and Spred1-2 proteins inhibit the activation of the ERK pathway elicited by cyclopentenone prostanoids.

Ejemplares similares