cAMP-activated Nr4a1 expression requires ERK activity and is modulated by MAPK phosphatase-1 in MA-10 Leydig cells.
Mol Cell Endocrinol
; 408: 45-52, 2015 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-25657047
ABSTRACT
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
AMP Cíclico
/
Proteína Quinasa 1 Activada por Mitógenos
/
Proteína Quinasa 3 Activada por Mitógenos
/
Fosfatasa 1 de Especificidad Dual
/
Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares
/
Células Intersticiales del Testículo
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Mol Cell Endocrinol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Argentina