STAT5 Is Essential for Akt/p70S6 Kinase Activity during IL-2-Induced Lymphocyte Proliferation
In: The Journal of Immunology, Jg. 179 (2007-10-15), S. 5301-5308
Online
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Zugriff:
IL-2R activates two distinct signaling pathways mediated by the adaptor protein Shc and the transcription factor STAT5. Prior mutagenesis studies of the IL-2R have indicated that the Shc and STAT5 pathways are redundant in the ability to induce lymphocyte proliferation. Yet paradoxically, T cells from STAT5-deficient mice fail to proliferate in response to IL-2, suggesting that the Shc pathway is unable to promote mitogenesis in the genetic absence of STAT5. Here we show in the murine lymphocyte cell line Ba/F3 that low levels of STAT5 activity are essential for Shc signaling. In the absence of STAT5 activity, Shc was unable to sustain activation of the Akt/p70S6 kinase pathway or promote lymphocyte proliferation and viability. Restoring STAT5 activity via a heterologous receptor rescued Shc-induced Akt/p70S6 kinase activity and cell proliferation with kinetics consistent with a transcriptional mechanism. Thus, STAT5 appears to regulate the expression of one or more unidentified components of the Akt pathway. Our results not only explain the severe proliferative defect in STAT5-deficient T cells but also provide mechanistic insight into the oncogenic properties of STAT5 in various leukemias and lymphomas.
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STAT5 Is Essential for Akt/p70S6 Kinase Activity during IL-2-Induced Lymphocyte Proliferation
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Autor/in / Beteiligte Person: | Lockyer, Heather M. ; Tran, Eric ; Nelson, Brad H. |
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Zeitschrift: | The Journal of Immunology, Jg. 179 (2007-10-15), S. 5301-5308 |
Veröffentlichung: | The American Association of Immunologists, 2007 |
Medientyp: | unknown |
ISSN: | 1550-6606 (print) ; 0022-1767 (print) |
DOI: | 10.4049/jimmunol.179.8.5301 |
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