| First Author | Lazorchak AS | Year | 2010 |
| Journal | Mol Cell | Volume | 39 |
| Issue | 3 | Pages | 433-43 |
| PubMed ID | 20705244 | Mgi Jnum | J:163678 |
| Mgi Id | MGI:4829421 | Doi | 10.1016/j.molcel.2010.07.031 |
| Citation | Lazorchak AS, et al. (2010) Sin1-mTORC2 suppresses rag and il7r gene expression through Akt2 in B cells. Mol Cell 39(3):433-43 |
| abstractText | Mammalian target of rapamycin (mTOR) is an important mediator of phosphoinositol-3-kinase (PI3K) signaling. PI3K signaling regulates B cell development, homeostasis, and immune responses. However, the function and molecular mechanism of mTOR-mediated PI3K signaling in B cells has not been fully elucidated. Here we show that Sin1, an essential component of mTOR complex 2 (mTORC2), regulates B cell development. Sin1 deficiency results in increased IL-7 receptor (il7r) and RAG recombinase (rag1 and rag2) gene expression, leading to enhanced pro-B cell survival and augmented V(D)J recombinase activity. We further show that Akt2 specifically mediates the Sin1-mTORC2 dependent suppression of il7r and rag gene expression in B cells by regulating FoxO1 phosphorylation. Finally, we demonstrate that the mTOR inhibitor rapamycin induces rag expression and promotes V(D)J recombination in B cells. Our study reveals that the Sin1/mTORC2-Akt2 signaling axis is a key regulator of FoxO1 transcriptional activity in B cells. |
