Two distinct interleukin-3-mediated signal pathways, Ras-NFIL3 (E4BP4) and Bcl-xL, regulate the survival of murine pro-B lymphocytes.
Mol Cell Biol
; 19(4): 2754-62, 1999 Apr.
Article
em En
| MEDLINE
| ID: mdl-10082541
ABSTRACT
Hematopoietic cells require cytokine-initiated signals for survival as well as proliferation. The pathways that transduce these signals, ensuring timely regulation of cell fate genes, remain largely undefined. The NFIL3 (E4BP4) transcription factor, Bcl-xL, and constitutively active mutants of components in Ras signal transduction pathways have been identified as key regulation proteins affecting murine interleukin-3 (IL-3)-dependent cell survival. Here we show that expression of NFIL3 is regulated by oncogenic Ras mutants through both the Raf-mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways. NFIL3 inhibits apoptosis without affecting Bcl-xL expression. By contrast, Bcl-xL levels are regulated through the membrane proximal portion in the cytoplasmic domain of the receptor (betac chain), which is shared by IL-3 and granulocyte-macrophage colony-stimulating factor. Activation of either pathway alone is insufficient to ensure cell survival, indicating that multiple independent signal transduction pathways mediate the survival of developing B-lymphoid cells.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Células-Tronco Hematopoéticas
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Linfócitos B
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Interleucina-3
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Apoptose
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Proteínas Proto-Oncogênicas c-bcl-2
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Proteínas de Ligação a DNA
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article