The AGC kinase serum- and glucocorticoid-regulated kinase 1 (SGK1) regulates T(H)1 and T(H)2 differentiation downstream of mTORC2

Serum- and glucocorticoid-regulated kinase 1 (SGK1) is an AGC kinase that regulates membrane sodium channel expression in renal tubular cells in an mTORC2-dependent manner. We hypothesized that SGK1 might represent a novel mTORC2-dependent regulator of T cell differentiation and function. Here we demonstrate that upon activation by mTORC2, SGK1 promoted T(H)2 differentiation by negatively regulating the NEDD4-2 E3 ligase-mediated destruction of transcription factor JunB. Simultaneously, SGK1 repressed the production of interferon-γ (IFN-γ) by controlling the expression of the long isoform of transcription factor TCF-1. Consistent with these findings, mice with a selective deletion of SGK1 in T cells were resistant to experimentally induced asthma, generated robust amounts of IFN-γ in response to viral infections and more readily rejected tumors.