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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/15258
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oai:ri.conicet.gov.ar:11336/15258 |
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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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1846083477178417152 |
score |
13.22299 |