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cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cells.
Mori Sequeiros Garcia, Mercedes; Gorostizaga, Alejandra; Brion, Laura; González-Calvar, Silvia I; Paz, Cristina.
Afiliação
  • Mori Sequeiros Garcia M; Institute for Biomedical Research (INBIOMED), Department of Biochemistry, School of Medicine, University of Buenos Aires, Paraguay 2155, (C1121ABG), Buenos Aires, Argentina.
  • Gorostizaga A; Institute for Biomedical Research (INBIOMED), Department of Biochemistry, School of Medicine, University of Buenos Aires, Paraguay 2155, (C1121ABG), Buenos Aires, Argentina.
  • Brion L; Membrane Signaling Networks, Department of Medicine, Karolinska Institutet, CMM, Karolinska University Hospital-Solna, Solnavägen 1, 171 77 Solna, Stockholm, Sweden.
  • González-Calvar SI; Institute of Biology and Experimental Medicine, National Council for Scientific and Technical Research, Vuelta de Obligado 2490 (C1428DN), Buenos Aires, Argentina; School of Medicine, University of Buenos Aires, Paraguay 2155 (C1121ABG), Buenos Aires, Argentina.
  • Paz C; Institute for Biomedical Research (INBIOMED), Department of Biochemistry, School of Medicine, University of Buenos Aires, Paraguay 2155, (C1121ABG), Buenos Aires, Argentina. Electronic address: crispaz1506@gmail.com.
Mol Cell Endocrinol ; 408: 45-52, 2015 Jun 15.
Article em En | MEDLINE | ID: mdl-25657047
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: AMP Cíclico / Proteína Quinase 1 Ativada por Mitógeno / Proteína Quinase 3 Ativada por Mitógeno / Fosfatase 1 de Especificidade Dupla / Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares / Células Intersticiais do Testículo Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Mol Cell Endocrinol Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Argentina País de publicação: Irlanda
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: AMP Cíclico / Proteína Quinase 1 Ativada por Mitógeno / Proteína Quinase 3 Ativada por Mitógeno / Fosfatase 1 de Especificidade Dupla / Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares / Células Intersticiais do Testículo Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Mol Cell Endocrinol Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Argentina País de publicação: Irlanda