Mitogen-activated protein kinases p38 and ERK 1/2 mediate the wall stress-induced activation of GATA-4 binding in adult heart.
J Biol Chem
; 279(23): 24852-60, 2004 Jun 04.
Article
en En
| MEDLINE
| ID: mdl-15051723
ABSTRACT
The zinc finger transcription factor GATA-4 has been implicated as a critical regulator of inducible cardiac gene expression and as a potential mediator of the hypertrophic program. However, the precise intracellular mechanisms that regulate the DNA-binding activity of GATA-4 are not fully understood. The aim of the present study was to examine the role of mitogen-activated protein kinases (p38 kinase, extracellular signal-regulated protein kinase, and c-Jun N-terminal protein kinase) in the left ventricular wall stress-induced activation of GATA-4 DNA binding in adult heart. Isolated perfused rat hearts were subjected to increased left ventricular wall stress by inflating a balloon in the ventricle. Gel mobility shift assays were used to analyze the transacting factors that interact with the GATA motifs of the B-type natriuretic peptide promoter. The left ventricular wall stress rapidly activated GATA-4 DNA binding and significantly increased the levels of phosphorylated p38 kinase, extracellular signal-regulated protein kinase, and c-Jun N-terminal protein kinase. The wall stress-induced increase in the DNA-binding activity of GATA-4 was abolished both in the presence of the p38 inhibitor SB239063 and MEK1/2 inhibitor U0126. In contrast, the inhibition of c-Jun N-terminal protein kinase by CEP11004 had no effect on the baseline or stretch-induced GATA-4 DNA binding. Moreover, GATA-4 DNA binding was up-regulated by mechanical stretch in the isolated rat atria via p38 and extracellular signal-regulated protein kinase. In conclusion, the present study demonstrates that both p38 and extracellular signal-regulated protein kinase are required for the stretch-induced GATA-4 binding in intact heart.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Proteína Quinasa 1 Activada por Mitógenos
/
Proteínas Quinasas Activadas por Mitógenos
/
Proteínas de Unión al ADN
/
Miocardio
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2004
Tipo del documento:
Article
País de afiliación:
Finlandia