Two Distinct Interleukin-3-Mediated Signal Pathways, Ras-NFIL3 (E4BP4) and Bcl-xL, Regulate the Survival of Murine Pro-B Lymphocytes
| Autor: | Toshiya Inaba, Ryoko Kuribara, Takeshi Inukai, A. Thomas Look, Atsushi Miyajima, Taisei Kinoshita, Takao Yoshihara, Tetsuharu Shinjyo, Keiya Ozawa |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cell Survival
bcl-X Protein Apoptosis Bcl-xL Phosphatidylinositol 3-Kinases Cell fate determination Mice Animals Protein kinase A Cell Growth and Development Molecular Biology Transcription factor Interleukin 3 B-Lymphocytes Dose-Response Relationship Drug biology NFIL3 Models Immunological Cell Biology Hematopoietic Stem Cells Cell biology DNA-Binding Proteins Proto-Oncogene Proteins c-raf Basic-Leucine Zipper Transcription Factors G-Box Binding Factors Proto-Oncogene Proteins c-bcl-2 Calcium-Calmodulin-Dependent Protein Kinases ras Proteins biology.protein Interleukin-3 Signal transduction Signal Transduction Transcription Factors |
| Zdroj: | Molecular and Cellular Biology. 19:2754-2762 |
| ISSN: | 1098-5549 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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