| First Author | Stahl M | Year | 2002 |
| Journal | J Immunol | Volume | 168 |
| Issue | 10 | Pages | 5024-31 |
| PubMed ID | 11994454 | Mgi Jnum | J:76416 |
| Mgi Id | MGI:2179375 | Doi | 10.4049/jimmunol.168.10.5024 |
| Citation | Stahl M, et al. (2002) The Forkhead Transcription Factor FoxO Regulates Transcription of p27(Kip1) and Bim in Response to IL-2. J Immunol 168(10):5024-31 |
| abstractText | The cytokine IL-2 plays a very important role in the proliferation and survival of activated T cells. These effects of IL-2 are dependent on signaling through the phosphatidylinositol 3-kinase (PI3K) pathway. We and others have shown that PI3K, through activation of protein kinase B/Akt, inhibits transcriptional activation by a number of forkhead transcription factors (FoxO1, FoxO3, and FoxO4). In this study we have investigated the role of these forkhead transcription factors in the IL-2-induced T cell proliferation and survival. We show that IL-2 regulates phosphorylation of FoxO3 in a PI3K-dependent fashion. Phosphorylation and inactivation of FoxO3 appears to play an important role in IL-2-mediated T cell survival, because mere activation of FoxO3 is sufficient to trigger apoptosis in T cells. Indeed, active FoxO3 can induce expression of IL-2-regulated genes, such as the cdk inhibitor p27(Kip1) and the proapoptotic Bcl-2 family member Bim. Furthermore, we show that IL-2 triggers a rapid, PI3K-dependent, phosphorylation of FoxO1a in primary T cells. Thus, we propose that inactivation of FoxO transcription factors by IL-2 plays a critical role in T cell proliferation and survival. |
