Transcriptional regulation of tissue-specific genes by the ERK5 mitogen-activated protein kinase.
Mol Cell Biol
; 25(19): 8553-66, 2005 Oct.
Article
em En
| MEDLINE
| ID: mdl-16166637
ABSTRACT
The ERK5 mitogen-activated protein kinase (MAPK) differs from other MAPKs in possessing a potent transcriptional activation domain. ERK5-/- embryos die from angiogenic defects, but the precise physiological role of ERK5 remains poorly understood. To elucidate molecular functions of ERK5 in the development of vasculature and other tissues, we performed gene profile analyses of erk5-/- mouse embryos and erk5-/- fibroblast cells reconstituted with ERK5 or ERK5(1-740), which lacks the transactivation domain. These experiments revealed several potential ERK5 target genes, including a proapoptotic gene bnip3, known angiogenic genes flt1 and lklf (lung Krüppel-like factor), and genes that regulate cardiovascular development. Among these, LKLF, known for its roles in angiogenesis, T-cell quiescence, and survival, was found to be absolutely dependent on ERK5 for expression in endothelial and T cells. We show that ERK5 drives lklf transcription by activating MEF2 transcription factors. Expression of erk5 short hairpin or a dominant-negative form of the ERK5 upstream activator, MEK5, in T cells led to downregulation of LKLF, increased cell size and upregulation of activation markers. Thus, through its kinase and transcriptional activation domains, ERK5 regulates transcriptional responses of cell survival and quiescence critical for angiogenesis and T-cell function.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
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Regulação da Expressão Gênica
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Proteína Quinase 7 Ativada por Mitógeno
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Fatores de Transcrição Kruppel-Like
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos