cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cells

Autores
Mori Sequeiros, María de Las Mercedes; Gorostizaga, Alejandra Beatriz; Brion, Laura; Gónzalez Calvar, Silvia I.; Paz, Cristina del Valle
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In Leydig cells, LH and cAMP promote ERK1/2 activation and MAPK phosphatase-1 (MKP-1) induction. MKP-1 up-regulation, which involves post-translational modifications such as ERK1/2-mediated phosphorylation, reduces ERK1/2 phosphorylation as well as Steroidogenic Acute Regulatory (StAR) protein expression and steroidogenesis. As LH- and cAMP-promoted StAR transcription requires the induction of Nur77, product of Nr4a1 gene, we analyzed the roles of ERK1/2 and MKP-1 in 8Br–cAMP-mediated Nr4a1 expression in MA-10 Leydig cells. Pharmacological blockade of ERK1/2 activation partially reduced the 8Br–cAMP-mediated increase in both Nr4a1 messenger levels and promoter activity. MKP-1 knock-down increased 8Br–cAMP-induced promoter activity, while its over-expression produced the opposite effect. It is concluded that Nr4a1 induction is dependent on ERK1/2 and that MKP-1 negatively regulates this induction. Experiments based on the over-expression of MKP-1 mutated forms revealed that MKP-1 half life is determined by post-translational modifications in ERK-consensus sites, a regulation that modulates the effect of MKP-1 on Nr4a1 expression.
Fil: Mori Sequeiros, María de Las Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina
Fil: Gorostizaga, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina
Fil: Brion, Laura. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Karolinska University Hospital Solna. Karolinska Institutet; Suecia
Fil: Gónzalez Calvar, Silvia I.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Paz, Cristina del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina
Materia
Map Kinase Phosphatase
Mkp-1
Erk1/2
Nr4a1
Nur77
Leydig Cells
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/15258

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oai_identifier_str oai:ri.conicet.gov.ar:11336/15258
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cellsMori Sequeiros, María de Las MercedesGorostizaga, Alejandra BeatrizBrion, LauraGónzalez Calvar, Silvia I.Paz, Cristina del ValleMap Kinase PhosphataseMkp-1Erk1/2Nr4a1Nur77Leydig Cellshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In Leydig cells, LH and cAMP promote ERK1/2 activation and MAPK phosphatase-1 (MKP-1) induction. MKP-1 up-regulation, which involves post-translational modifications such as ERK1/2-mediated phosphorylation, reduces ERK1/2 phosphorylation as well as Steroidogenic Acute Regulatory (StAR) protein expression and steroidogenesis. As LH- and cAMP-promoted StAR transcription requires the induction of Nur77, product of Nr4a1 gene, we analyzed the roles of ERK1/2 and MKP-1 in 8Br–cAMP-mediated Nr4a1 expression in MA-10 Leydig cells. Pharmacological blockade of ERK1/2 activation partially reduced the 8Br–cAMP-mediated increase in both Nr4a1 messenger levels and promoter activity. MKP-1 knock-down increased 8Br–cAMP-induced promoter activity, while its over-expression produced the opposite effect. It is concluded that Nr4a1 induction is dependent on ERK1/2 and that MKP-1 negatively regulates this induction. Experiments based on the over-expression of MKP-1 mutated forms revealed that MKP-1 half life is determined by post-translational modifications in ERK-consensus sites, a regulation that modulates the effect of MKP-1 on Nr4a1 expression.Fil: Mori Sequeiros, María de Las Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; ArgentinaFil: Gorostizaga, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; ArgentinaFil: Brion, Laura. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Karolinska University Hospital Solna. Karolinska Institutet; SueciaFil: Gónzalez Calvar, Silvia I.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Paz, Cristina del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; ArgentinaElsevier Ireland2015-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/15258Mori Sequeiros, María de Las Mercedes; Gorostizaga, Alejandra Beatriz; Brion, Laura; Gónzalez Calvar, Silvia I.; Paz, Cristina del Valle; cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cells; Elsevier Ireland; Molecular and Cellular Endocrinology; 408; 6-2015; 45-520303-7207enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0303720715000659info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mce.2015.01.041info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:34:57Zoai:ri.conicet.gov.ar:11336/15258instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:34:57.93CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cells
title cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cells
spellingShingle cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cells
Mori Sequeiros, María de Las Mercedes
Map Kinase Phosphatase
Mkp-1
Erk1/2
Nr4a1
Nur77
Leydig Cells
title_short cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cells
title_full cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cells
title_fullStr cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cells
title_full_unstemmed cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cells
title_sort cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cells
dc.creator.none.fl_str_mv Mori Sequeiros, María de Las Mercedes
Gorostizaga, Alejandra Beatriz
Brion, Laura
Gónzalez Calvar, Silvia I.
Paz, Cristina del Valle
author Mori Sequeiros, María de Las Mercedes
author_facet Mori Sequeiros, María de Las Mercedes
Gorostizaga, Alejandra Beatriz
Brion, Laura
Gónzalez Calvar, Silvia I.
Paz, Cristina del Valle
author_role author
author2 Gorostizaga, Alejandra Beatriz
Brion, Laura
Gónzalez Calvar, Silvia I.
Paz, Cristina del Valle
author2_role author
author
author
author
dc.subject.none.fl_str_mv Map Kinase Phosphatase
Mkp-1
Erk1/2
Nr4a1
Nur77
Leydig Cells
topic Map Kinase Phosphatase
Mkp-1
Erk1/2
Nr4a1
Nur77
Leydig Cells
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In Leydig cells, LH and cAMP promote ERK1/2 activation and MAPK phosphatase-1 (MKP-1) induction. MKP-1 up-regulation, which involves post-translational modifications such as ERK1/2-mediated phosphorylation, reduces ERK1/2 phosphorylation as well as Steroidogenic Acute Regulatory (StAR) protein expression and steroidogenesis. As LH- and cAMP-promoted StAR transcription requires the induction of Nur77, product of Nr4a1 gene, we analyzed the roles of ERK1/2 and MKP-1 in 8Br–cAMP-mediated Nr4a1 expression in MA-10 Leydig cells. Pharmacological blockade of ERK1/2 activation partially reduced the 8Br–cAMP-mediated increase in both Nr4a1 messenger levels and promoter activity. MKP-1 knock-down increased 8Br–cAMP-induced promoter activity, while its over-expression produced the opposite effect. It is concluded that Nr4a1 induction is dependent on ERK1/2 and that MKP-1 negatively regulates this induction. Experiments based on the over-expression of MKP-1 mutated forms revealed that MKP-1 half life is determined by post-translational modifications in ERK-consensus sites, a regulation that modulates the effect of MKP-1 on Nr4a1 expression.
Fil: Mori Sequeiros, María de Las Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina
Fil: Gorostizaga, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina
Fil: Brion, Laura. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Karolinska University Hospital Solna. Karolinska Institutet; Suecia
Fil: Gónzalez Calvar, Silvia I.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Paz, Cristina del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica; Argentina
description In Leydig cells, LH and cAMP promote ERK1/2 activation and MAPK phosphatase-1 (MKP-1) induction. MKP-1 up-regulation, which involves post-translational modifications such as ERK1/2-mediated phosphorylation, reduces ERK1/2 phosphorylation as well as Steroidogenic Acute Regulatory (StAR) protein expression and steroidogenesis. As LH- and cAMP-promoted StAR transcription requires the induction of Nur77, product of Nr4a1 gene, we analyzed the roles of ERK1/2 and MKP-1 in 8Br–cAMP-mediated Nr4a1 expression in MA-10 Leydig cells. Pharmacological blockade of ERK1/2 activation partially reduced the 8Br–cAMP-mediated increase in both Nr4a1 messenger levels and promoter activity. MKP-1 knock-down increased 8Br–cAMP-induced promoter activity, while its over-expression produced the opposite effect. It is concluded that Nr4a1 induction is dependent on ERK1/2 and that MKP-1 negatively regulates this induction. Experiments based on the over-expression of MKP-1 mutated forms revealed that MKP-1 half life is determined by post-translational modifications in ERK-consensus sites, a regulation that modulates the effect of MKP-1 on Nr4a1 expression.
publishDate 2015
dc.date.none.fl_str_mv 2015-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/15258
Mori Sequeiros, María de Las Mercedes; Gorostizaga, Alejandra Beatriz; Brion, Laura; Gónzalez Calvar, Silvia I.; Paz, Cristina del Valle; cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cells; Elsevier Ireland; Molecular and Cellular Endocrinology; 408; 6-2015; 45-52
0303-7207
url http://hdl.handle.net/11336/15258
identifier_str_mv Mori Sequeiros, María de Las Mercedes; Gorostizaga, Alejandra Beatriz; Brion, Laura; Gónzalez Calvar, Silvia I.; Paz, Cristina del Valle; cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cells; Elsevier Ireland; Molecular and Cellular Endocrinology; 408; 6-2015; 45-52
0303-7207
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0303720715000659
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mce.2015.01.041
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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