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Nat Immunol. 2014 May;15(5):457-64. doi: 10.1038/ni.2867. Epub 2014 Apr 6.

The AGC kinase SGK1 regulates TH1 and TH2 differentiation downstream of the mTORC2 complex.

Author information

1
Sidney Kimmel Comprehensive Cancer Research Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
2
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
3
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
4
Immune Cells and Inflammation Section, Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
5
Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire, USA.

Abstract

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-γ (IFN-γ) 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-γ in response to viral infection and more readily rejected tumors.

PMID:
24705297
PMCID:
PMC4267697
DOI:
10.1038/ni.2867
[Indexed for MEDLINE]
Free PMC Article

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