First Author | Grumont RJ | Year | 2002 |
Journal | Mol Cell | Volume | 10 |
Issue | 6 | Pages | 1283-94 |
PubMed ID | 12504005 | Mgi Jnum | J:125671 |
Mgi Id | MGI:3759386 | Doi | 10.1016/s1097-2765(02)00779-7 |
Citation | Grumont RJ, et al. (2002) B cell growth is controlled by phosphatidylinosotol 3-kinase-dependent induction of Rel/NF-kappaB regulated c-myc transcription. Mol Cell 10(6):1283-94 |
abstractText | Rel/NF-kappaB transcription factors regulate the division and survival of B lymphocytes. Here we show that B cells lacking NF-kappaB1 and c-Rel fail to increase in size upon mitogenic stimulation due to a reduction in induced c-myc expression. Mitogen-induced B cell growth, although not markedly impaired by FRAP/mTOR or MEK inhibitors, required phosphatidylinositol 3-kinase (PI3K) activity. Inhibition of PI3K-dependent growth coincided with a block in the nuclear import of NF-kappaB1/c-Rel dimers and a failure to upregulate c-myc. In addition, PI3K was shown to be necessary for a transcription-independent increase in c-Myc protein levels that accompanies mitogenic activation. Collectively, these findings establish a role for Rel/NF-kappaB signaling in the mitogen-induced growth of mammalian cells, which in B lymphocytes requires a PI3K/c-myc-dependent pathway. |