Hormonal activation of a kinase cascade localized at the mitochondria is required for StAR protein activity

Autores
Poderoso, Cecilia; Maloberti, Paula Mariana; Duarte, Alejandra Beatriz; Neuman, Maria Isabel; Paz, Cristina del Valle; Cornejo Maciel, Maria Fabiana; Podesta, Ernesto Jorge
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
It is known that ERK1/2 and MEK1/2 participate in the regulation of Star gene transcription. However, their role in StAR protein post-transcriptional regulation is not described yet. In this study we analyzed the relationship between the MAPK cascade and StAR protein phosphorylation and function. We have demonstrated that (a) steroidogenesis in MA-10 Leydig cells depends on the specific of ERK1/2 activation at the mitochondria; (b) ERK1/2 phosphorylation is driven by mitochondrial PKA and constitutive MEK1/2 in this organelle; (c) active ERK1/2 interacts with StAR protein, leads to StAR protein phosphorylation at Ser(232) only in the presence of cholesterol; (d) directed mutagenesis of Ser(232) (S232A) inhibited in vitro StAR protein phosphorylation by ERK1; (e) transient transfection of MA-10 cells with StAR S232A cDNA markedly reduced the yield of progesterone production. We show that StAR protein is a substrate of ERK1/2, and that mitochondrial ERK1/2 is part of a multimeric complex that regulates cholesterol transport.
Fil: Poderoso, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Maloberti, Paula Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Duarte, Alejandra Beatriz. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Neuman, Maria Isabel. 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. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Cornejo Maciel, Maria Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Materia
CHOLESTEROL TRANSPORT
ERK1/2
MEK1/2
PKA
PROTEIN PHOSPHORYLATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/136906

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hormonal activation of a kinase cascade localized at the mitochondria is required for StAR protein activityPoderoso, CeciliaMaloberti, Paula MarianaDuarte, Alejandra BeatrizNeuman, Maria IsabelPaz, Cristina del ValleCornejo Maciel, Maria FabianaPodesta, Ernesto JorgeCHOLESTEROL TRANSPORTERK1/2MEK1/2PKAPROTEIN PHOSPHORYLATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1It is known that ERK1/2 and MEK1/2 participate in the regulation of Star gene transcription. However, their role in StAR protein post-transcriptional regulation is not described yet. In this study we analyzed the relationship between the MAPK cascade and StAR protein phosphorylation and function. We have demonstrated that (a) steroidogenesis in MA-10 Leydig cells depends on the specific of ERK1/2 activation at the mitochondria; (b) ERK1/2 phosphorylation is driven by mitochondrial PKA and constitutive MEK1/2 in this organelle; (c) active ERK1/2 interacts with StAR protein, leads to StAR protein phosphorylation at Ser(232) only in the presence of cholesterol; (d) directed mutagenesis of Ser(232) (S232A) inhibited in vitro StAR protein phosphorylation by ERK1; (e) transient transfection of MA-10 cells with StAR S232A cDNA markedly reduced the yield of progesterone production. We show that StAR protein is a substrate of ERK1/2, and that mitochondrial ERK1/2 is part of a multimeric complex that regulates cholesterol transport.Fil: Poderoso, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Maloberti, Paula Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Duarte, Alejandra Beatriz. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Neuman, Maria Isabel. 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. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Cornejo Maciel, Maria Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaElsevier Ireland2009-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/136906Poderoso, Cecilia; Maloberti, Paula Mariana; Duarte, Alejandra Beatriz; Neuman, Maria Isabel; Paz, Cristina del Valle; et al.; Hormonal activation of a kinase cascade localized at the mitochondria is required for StAR protein activity; Elsevier Ireland; Molecular and Cellular Endocrinology; 300; 1-2; 12-2009; 37-420303-7207CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0303720708004693info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mce.2008.10.009info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:02:30Zoai:ri.conicet.gov.ar:11336/136906instacron: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:34982025-10-22 12:02:30.583CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hormonal activation of a kinase cascade localized at the mitochondria is required for StAR protein activity
title Hormonal activation of a kinase cascade localized at the mitochondria is required for StAR protein activity
spellingShingle Hormonal activation of a kinase cascade localized at the mitochondria is required for StAR protein activity
Poderoso, Cecilia
CHOLESTEROL TRANSPORT
ERK1/2
MEK1/2
PKA
PROTEIN PHOSPHORYLATION
title_short Hormonal activation of a kinase cascade localized at the mitochondria is required for StAR protein activity
title_full Hormonal activation of a kinase cascade localized at the mitochondria is required for StAR protein activity
title_fullStr Hormonal activation of a kinase cascade localized at the mitochondria is required for StAR protein activity
title_full_unstemmed Hormonal activation of a kinase cascade localized at the mitochondria is required for StAR protein activity
title_sort Hormonal activation of a kinase cascade localized at the mitochondria is required for StAR protein activity
dc.creator.none.fl_str_mv Poderoso, Cecilia
Maloberti, Paula Mariana
Duarte, Alejandra Beatriz
Neuman, Maria Isabel
Paz, Cristina del Valle
Cornejo Maciel, Maria Fabiana
Podesta, Ernesto Jorge
author Poderoso, Cecilia
author_facet Poderoso, Cecilia
Maloberti, Paula Mariana
Duarte, Alejandra Beatriz
Neuman, Maria Isabel
Paz, Cristina del Valle
Cornejo Maciel, Maria Fabiana
Podesta, Ernesto Jorge
author_role author
author2 Maloberti, Paula Mariana
Duarte, Alejandra Beatriz
Neuman, Maria Isabel
Paz, Cristina del Valle
Cornejo Maciel, Maria Fabiana
Podesta, Ernesto Jorge
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CHOLESTEROL TRANSPORT
ERK1/2
MEK1/2
PKA
PROTEIN PHOSPHORYLATION
topic CHOLESTEROL TRANSPORT
ERK1/2
MEK1/2
PKA
PROTEIN PHOSPHORYLATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv It is known that ERK1/2 and MEK1/2 participate in the regulation of Star gene transcription. However, their role in StAR protein post-transcriptional regulation is not described yet. In this study we analyzed the relationship between the MAPK cascade and StAR protein phosphorylation and function. We have demonstrated that (a) steroidogenesis in MA-10 Leydig cells depends on the specific of ERK1/2 activation at the mitochondria; (b) ERK1/2 phosphorylation is driven by mitochondrial PKA and constitutive MEK1/2 in this organelle; (c) active ERK1/2 interacts with StAR protein, leads to StAR protein phosphorylation at Ser(232) only in the presence of cholesterol; (d) directed mutagenesis of Ser(232) (S232A) inhibited in vitro StAR protein phosphorylation by ERK1; (e) transient transfection of MA-10 cells with StAR S232A cDNA markedly reduced the yield of progesterone production. We show that StAR protein is a substrate of ERK1/2, and that mitochondrial ERK1/2 is part of a multimeric complex that regulates cholesterol transport.
Fil: Poderoso, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Maloberti, Paula Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Duarte, Alejandra Beatriz. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Neuman, Maria Isabel. 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. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Cornejo Maciel, Maria Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
description It is known that ERK1/2 and MEK1/2 participate in the regulation of Star gene transcription. However, their role in StAR protein post-transcriptional regulation is not described yet. In this study we analyzed the relationship between the MAPK cascade and StAR protein phosphorylation and function. We have demonstrated that (a) steroidogenesis in MA-10 Leydig cells depends on the specific of ERK1/2 activation at the mitochondria; (b) ERK1/2 phosphorylation is driven by mitochondrial PKA and constitutive MEK1/2 in this organelle; (c) active ERK1/2 interacts with StAR protein, leads to StAR protein phosphorylation at Ser(232) only in the presence of cholesterol; (d) directed mutagenesis of Ser(232) (S232A) inhibited in vitro StAR protein phosphorylation by ERK1; (e) transient transfection of MA-10 cells with StAR S232A cDNA markedly reduced the yield of progesterone production. We show that StAR protein is a substrate of ERK1/2, and that mitochondrial ERK1/2 is part of a multimeric complex that regulates cholesterol transport.
publishDate 2009
dc.date.none.fl_str_mv 2009-12
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/11336/136906
Poderoso, Cecilia; Maloberti, Paula Mariana; Duarte, Alejandra Beatriz; Neuman, Maria Isabel; Paz, Cristina del Valle; et al.; Hormonal activation of a kinase cascade localized at the mitochondria is required for StAR protein activity; Elsevier Ireland; Molecular and Cellular Endocrinology; 300; 1-2; 12-2009; 37-42
0303-7207
CONICET Digital
CONICET
url http://hdl.handle.net/11336/136906
identifier_str_mv Poderoso, Cecilia; Maloberti, Paula Mariana; Duarte, Alejandra Beatriz; Neuman, Maria Isabel; Paz, Cristina del Valle; et al.; Hormonal activation of a kinase cascade localized at the mitochondria is required for StAR protein activity; Elsevier Ireland; Molecular and Cellular Endocrinology; 300; 1-2; 12-2009; 37-42
0303-7207
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0303720708004693
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.mce.2008.10.009
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
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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