Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4

Autores
Cooke, Mariana; Orlando, Ulises Daniel; Maloberti, Paula Mariana; Podesta, Ernesto Jorge; Cornejo Maciel, Maria Fabiana
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Acyl-CoA synthetase 4 (ACSL4) is implicated in fatty acid metabolism with marked preference for arachidonic acid (AA). ACSL4 plays crucial roles in physiological functions such as steroid synthesis and in pathological processes such as tumorigenesis. However, factors regulating ACSL4 mRNA and/or protein levels are not fully described. Because ACSL4 protein expression requires tyrosine phosphatase activity, in this study we aimed to identify the tyrosine phosphatase involved in ACSL4 expression. NSC87877, a specific inhibitor of the tyrosine phosphatase SHP2, reduced ACSL4 protein levels in ACSL4-rich breast cancer cells and steroidogenic cells. Indeed, overexpression of an active form of SHP2 increased ACSL4 protein levels in MA-10 Leydig steroidogenic cells. SHP2 has to be activated through a cAMP-dependent pathway to exert its effect on ACSL4. The effects could be specifically attributed to SHP2 because knockdown of the phosphatase reduced ACSL4 mRNA and protein levels. Through the action on ACSL4 protein levels, SHP2 affected AA-CoA production and metabolism and, finally, the steroidogenic capacity of MA-10 cells: overexpression (or knockdown) of SHP2 led to increased (or decreased) steroid production. We describe for the first time the involvement of SHP2 activity in the regulation of the expression of the fatty acid-metabolizing enzyme ACSL4.
Fil: Cooke, Mariana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Orlando, Ulises Daniel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Maloberti, Paula Mariana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Podesta, Ernesto Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Cornejo Maciel, Maria Fabiana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Materia
ARACHIDONIC ACID
BREAST CANCER CELLS
LEYDIG CELLS
LONG-CHAIN ACYL-COA SYNTHETASES
PROLIFERATION
PROTEIN TYROSINE PHOSPHATASES
STEROIDOGENESIS
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:11336/112906
Acceder
id CONICETDig_1fe1feb594a3b40ecbe36d5a817d3e96
oai_identifier_str oai:ri.conicet.gov.ar:11336/112906
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4Cooke, MarianaOrlando, Ulises DanielMaloberti, Paula MarianaPodesta, Ernesto JorgeCornejo Maciel, Maria FabianaARACHIDONIC ACIDBREAST CANCER CELLSLEYDIG CELLSLONG-CHAIN ACYL-COA SYNTHETASESPROLIFERATIONPROTEIN TYROSINE PHOSPHATASESSTEROIDOGENESIShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Acyl-CoA synthetase 4 (ACSL4) is implicated in fatty acid metabolism with marked preference for arachidonic acid (AA). ACSL4 plays crucial roles in physiological functions such as steroid synthesis and in pathological processes such as tumorigenesis. However, factors regulating ACSL4 mRNA and/or protein levels are not fully described. Because ACSL4 protein expression requires tyrosine phosphatase activity, in this study we aimed to identify the tyrosine phosphatase involved in ACSL4 expression. NSC87877, a specific inhibitor of the tyrosine phosphatase SHP2, reduced ACSL4 protein levels in ACSL4-rich breast cancer cells and steroidogenic cells. Indeed, overexpression of an active form of SHP2 increased ACSL4 protein levels in MA-10 Leydig steroidogenic cells. SHP2 has to be activated through a cAMP-dependent pathway to exert its effect on ACSL4. The effects could be specifically attributed to SHP2 because knockdown of the phosphatase reduced ACSL4 mRNA and protein levels. Through the action on ACSL4 protein levels, SHP2 affected AA-CoA production and metabolism and, finally, the steroidogenic capacity of MA-10 cells: overexpression (or knockdown) of SHP2 led to increased (or decreased) steroid production. We describe for the first time the involvement of SHP2 activity in the regulation of the expression of the fatty acid-metabolizing enzyme ACSL4.Fil: Cooke, Mariana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Orlando, Ulises Daniel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Maloberti, Paula Mariana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Podesta, Ernesto Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Cornejo Maciel, Maria Fabiana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaAmerican Society for Biochemistry and Molecular Biology2011-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/112906Cooke, Mariana; Orlando, Ulises Daniel; Maloberti, Paula Mariana; Podesta, Ernesto Jorge; Cornejo Maciel, Maria Fabiana; Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4; American Society for Biochemistry and Molecular Biology; Journal of Lipid Research Papers In Press; 52; 11; 11-2011; 1936-19480022-22751539-7262CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.jlr.org/content/52/11/1936.longinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196225/info:eu-repo/semantics/altIdentifier/doi/10.1194/jlr.M015552info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:43:30Zoai:ri.conicet.gov.ar:11336/112906instacron: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:34982025-09-03 09:43:30.526CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4
title Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4
spellingShingle Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4
Cooke, Mariana
ARACHIDONIC ACID
BREAST CANCER CELLS
LEYDIG CELLS
LONG-CHAIN ACYL-COA SYNTHETASES
PROLIFERATION
PROTEIN TYROSINE PHOSPHATASES
STEROIDOGENESIS
title_short Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4
title_full Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4
title_fullStr Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4
title_full_unstemmed Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4
title_sort Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4
dc.creator.none.fl_str_mv Cooke, Mariana
Orlando, Ulises Daniel
Maloberti, Paula Mariana
Podesta, Ernesto Jorge
Cornejo Maciel, Maria Fabiana
author Cooke, Mariana
author_facet Cooke, Mariana
Orlando, Ulises Daniel
Maloberti, Paula Mariana
Podesta, Ernesto Jorge
Cornejo Maciel, Maria Fabiana
author_role author
author2 Orlando, Ulises Daniel
Maloberti, Paula Mariana
Podesta, Ernesto Jorge
Cornejo Maciel, Maria Fabiana
author2_role author
author
author
author
dc.subject.none.fl_str_mv ARACHIDONIC ACID
BREAST CANCER CELLS
LEYDIG CELLS
LONG-CHAIN ACYL-COA SYNTHETASES
PROLIFERATION
PROTEIN TYROSINE PHOSPHATASES
STEROIDOGENESIS
topic ARACHIDONIC ACID
BREAST CANCER CELLS
LEYDIG CELLS
LONG-CHAIN ACYL-COA SYNTHETASES
PROLIFERATION
PROTEIN TYROSINE PHOSPHATASES
STEROIDOGENESIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Acyl-CoA synthetase 4 (ACSL4) is implicated in fatty acid metabolism with marked preference for arachidonic acid (AA). ACSL4 plays crucial roles in physiological functions such as steroid synthesis and in pathological processes such as tumorigenesis. However, factors regulating ACSL4 mRNA and/or protein levels are not fully described. Because ACSL4 protein expression requires tyrosine phosphatase activity, in this study we aimed to identify the tyrosine phosphatase involved in ACSL4 expression. NSC87877, a specific inhibitor of the tyrosine phosphatase SHP2, reduced ACSL4 protein levels in ACSL4-rich breast cancer cells and steroidogenic cells. Indeed, overexpression of an active form of SHP2 increased ACSL4 protein levels in MA-10 Leydig steroidogenic cells. SHP2 has to be activated through a cAMP-dependent pathway to exert its effect on ACSL4. The effects could be specifically attributed to SHP2 because knockdown of the phosphatase reduced ACSL4 mRNA and protein levels. Through the action on ACSL4 protein levels, SHP2 affected AA-CoA production and metabolism and, finally, the steroidogenic capacity of MA-10 cells: overexpression (or knockdown) of SHP2 led to increased (or decreased) steroid production. We describe for the first time the involvement of SHP2 activity in the regulation of the expression of the fatty acid-metabolizing enzyme ACSL4.
Fil: Cooke, Mariana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Orlando, Ulises Daniel. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Maloberti, Paula Mariana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Podesta, Ernesto Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Cornejo Maciel, Maria Fabiana. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
description Acyl-CoA synthetase 4 (ACSL4) is implicated in fatty acid metabolism with marked preference for arachidonic acid (AA). ACSL4 plays crucial roles in physiological functions such as steroid synthesis and in pathological processes such as tumorigenesis. However, factors regulating ACSL4 mRNA and/or protein levels are not fully described. Because ACSL4 protein expression requires tyrosine phosphatase activity, in this study we aimed to identify the tyrosine phosphatase involved in ACSL4 expression. NSC87877, a specific inhibitor of the tyrosine phosphatase SHP2, reduced ACSL4 protein levels in ACSL4-rich breast cancer cells and steroidogenic cells. Indeed, overexpression of an active form of SHP2 increased ACSL4 protein levels in MA-10 Leydig steroidogenic cells. SHP2 has to be activated through a cAMP-dependent pathway to exert its effect on ACSL4. The effects could be specifically attributed to SHP2 because knockdown of the phosphatase reduced ACSL4 mRNA and protein levels. Through the action on ACSL4 protein levels, SHP2 affected AA-CoA production and metabolism and, finally, the steroidogenic capacity of MA-10 cells: overexpression (or knockdown) of SHP2 led to increased (or decreased) steroid production. We describe for the first time the involvement of SHP2 activity in the regulation of the expression of the fatty acid-metabolizing enzyme ACSL4.
publishDate 2011
dc.date.none.fl_str_mv 2011-11
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/11336/112906
Cooke, Mariana; Orlando, Ulises Daniel; Maloberti, Paula Mariana; Podesta, Ernesto Jorge; Cornejo Maciel, Maria Fabiana; Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4; American Society for Biochemistry and Molecular Biology; Journal of Lipid Research Papers In Press; 52; 11; 11-2011; 1936-1948
0022-2275
1539-7262
CONICET Digital
CONICET
url http://hdl.handle.net/11336/112906
identifier_str_mv Cooke, Mariana; Orlando, Ulises Daniel; Maloberti, Paula Mariana; Podesta, Ernesto Jorge; Cornejo Maciel, Maria Fabiana; Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4; American Society for Biochemistry and Molecular Biology; Journal of Lipid Research Papers In Press; 52; 11; 11-2011; 1936-1948
0022-2275
1539-7262
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.jlr.org/content/52/11/1936.long
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3196225/
info:eu-repo/semantics/altIdentifier/doi/10.1194/jlr.M015552
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
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
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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score 13.13397

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