A novel mechanism for ERK-dependent regulation of IL4 transcription during human Th2-cell differentiation.
Immunol Cell Biol
; 90(7): 676-87, 2012 Aug.
Article
em En
| MEDLINE
| ID: mdl-21989417
ABSTRACT
We demonstrate that the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK)-1 and ERK-2 have a central role in mediating T-cell receptor-dependent induction of IL4 expression in human CD4(+) T cells. Significantly, this involved a novel mechanism wherein receptor cross-linking induced activated ERK to physically associate with a promoter element on the IL4 gene. The proximally localized ERK then facilitated recruitment of the key transcription factors necessary for initiating IL4 gene transcription. Although both ERK-1 and ERK-2 bound to the promoter, recruitment of either one alone was found to be sufficient. We thus identify a novel mode of function for ERK wherein its physical association with the promoter serves as a prerequisite for enhanceosome assembly. This unusual pathway is also indispensable for human Th2-cell differentiation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Diferenciação Celular
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Interleucina-4
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Células Th2
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Proteína Quinase 1 Ativada por Mitógeno
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Proteína Quinase 3 Ativada por Mitógeno
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article