Cytokine-induced myeloid differentiation is dependent on activation of the MEK/ERK pathway.
Leuk Res
; 29(11): 1293-306, 2005 Nov.
Article
em En
| MEDLINE
| ID: mdl-16164983
ABSTRACT
The intracellular signaling pathways that mediate cytokine-induced granulocytic and monocytic differentiation are incompletely understood. In this study, we examined the importance of the MEK/ERK signal transduction pathway in granulocyte-colony stimulating factor (G-CSF)-induced granulocytic differentiation of murine 32 Dc l3 cells, and in interleukin-6 (IL-6)-induced monocytic differentiation of murine M1 cells. Induction of granulocytic differentiation with G-CSF, or monocytic differentiation with IL-6, led to rapid and sustained activation of the MEK-1/-2 and ERK-1/-2 enzymes. Inhibition of the MEK/ERK pathway by pretreatment with the MEK inhibitor U 0126 dramatically attenuated G-CSF-induced granulocytic differentiation and IL-6-induced monocytic differentiation. Inhibition of MEK/ERK signaling also significantly reduced cytokine-induced DNA binding activities of STAT 3 and PU.1, transcription factors that have been implicated in myeloid differentiation. Additionally, interleukin-3, which inhibits G-CSF-induced differentiation of 32 Dc l3 cells, also inhibited the ability of G-CSF to stimulate prolonged MEK/ERK activation. Thus, the opposing actions of different hematopoietic cytokines on myeloid progenitors may be mediated at the level of MEK/ERK activation. Taken together, these studies demonstrate an important requirement for MEK/ERK activation during cytokine-induced granulocytic and monocytic differentiation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Fator Estimulador de Colônias de Granulócitos
/
Interleucina-6
/
Sistema de Sinalização das MAP Quinases
/
Células Progenitoras Mieloides
/
MAP Quinases Reguladas por Sinal Extracelular
Limite:
Animals
Idioma:
En
Revista:
Leuk Res
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos