ERK3 promotes endothelial cell functions by upregulating SRC-3/SP1-mediated VEGFR2 expression.
J Cell Physiol
; 229(10): 1529-37, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-24585635
ABSTRACT
Despite a regain of interest recently in ERK3 kinase signaling, the molecular regulations of both ERK3 gene expression and protein kinase activity are still largely unknown. While it is shown that disruption of ERK3 gene causes neonatal lethality, cell type-specific functions of ERK3 signaling remain to be explored. In this study, we report that ERK3 gene expression is upregulated by cytokines through c-Jun in endothelial cells; c-Jun binds to the ERK3 gene and regulates its transcription. We further reveal a new role for ERK3 in regulating endothelial cell migration, proliferation and tube formation by upregulating SRC-3/SP-1-mediated VEGFR2 expression. The underlying molecular mechanism involves ERK3-stimulated formation of a transcriptional complex involving coactivator SRC-3, transcription factor SP-1 and the secondary coactivator CBP. Taken together, our study identified a molecular regulatory mechanism of ERK3 gene expression and revealed a previously unknown role of ERK3 in regulating endothelial cell functions.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fator de Transcrição Sp1
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Neovascularização Fisiológica
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Receptor 2 de Fatores de Crescimento do Endotélio Vascular
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Proteína Quinase 6 Ativada por Mitógeno
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Coativador 3 de Receptor Nuclear
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Células Endoteliais da Veia Umbilical Humana
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2014
Tipo de documento:
Article