IL-7 withdrawal induces a stress pathway activating p38 and Jun N-terminal kinases.
Cell Signal
; 14(9): 761-9, 2002 Sep.
Article
en En
| MEDLINE
| ID: mdl-12034357
ABSTRACT
IL-7 delivers survival signals to cells at an early stage in lymphoid development. In the absence of IL-7, pro-T cells undergo programmed cell death, which has previously been associated with a decline in Bcl-2 and translocation of Bax from cytosol to mitochondria. A new, earlier feature of IL-7 withdrawal was identified using an IL-7-dependent thymocyte line. We observed that withdrawal of IL-7 induced increased expression of jun and fos family member genes including c-jun, junB, junD, c-fos and fra2. This transient response peaked 3-4 h after IL-7 was withdrawn and resulted in increased DNA-binding activity of AP-1 and in a change in the composition of the Jun/Fos family dimers shown by electrophoretic mobility shift and supershift assays. Induction of jun and fos genes and the increased DNA-binding activity of AP-1 were attributable to the phosphorylation-induced activation of the stress kinases p38 and JNK and were blocked by the chemical kinase inhibitors SB203580 and SB202190. The stress response contributed to cell death following IL-7 withdrawal as shown by blocking the activity of the stress (MAP) kinases or by blocking the production of c-Jun and c-Fos using antisense oligonucleotides.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Interleucina-7
/
Proteínas Quinasas Activadas por Mitógenos
/
Sistema de Señalización de MAP Quinasas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Signal
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos