First Author | Heikamp EB | Year | 2014 |
Journal | Nat Immunol | Volume | 15 |
Issue | 5 | Pages | 457-64 |
PubMed ID | 24705297 | Mgi Jnum | J:209960 |
Mgi Id | MGI:5569179 | Doi | 10.1038/ni.2867 |
Citation | Heikamp EB, et al. (2014) The AGC kinase SGK1 regulates TH1 and TH2 differentiation downstream of the mTORC2 complex. Nat Immunol 15(5):457-64 |
abstractText | SGK1 is an AGC kinase that regulates the expression of membrane sodium channels in renal tubular cells in a manner dependent on the metabolic checkpoint kinase complex mTORC2. We hypothesized that SGK1 might represent an additional mTORC2-dependent regulator of the differentiation and function of T cells. Here we found that after activation by mTORC2, SGK1 promoted T helper type 2 (TH2) differentiation by negatively regulating degradation of the transcription factor JunB mediated by the E3 ligase Nedd4-2. Simultaneously, SGK1 repressed the production of interferon-gamma (IFN-gamma) by controlling expression of the long isoform of the transcription factor TCF-1. Consistent with those findings, mice with selective deletion of SGK1 in T cells were resistant to experimentally induced asthma, generated substantial IFN-gamma in response to viral infection and more readily rejected tumors. |