The AGC kinase SGK1 regulates T H 1 and T H 2 differentiation downstream of the mTORC2 complex

Emily B. Heikamp, Chirag H. Patel, Sam Collins, Adam Waickman, Min Hee Oh, Im Hong Sun, Peter Illei, Archna Sharma, Aniko Naray-Fejes-Toth, Geza Fejes-Toth, Jyoti Misra-Sen, Maureen R. Horton, Jonathan D. Powell

Research output: Contribution to journalArticle

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 (T H 2) 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.

Original languageEnglish (US)
Pages (from-to)457-464
Number of pages8
JournalNature Immunology
Volume15
Issue number5
DOIs
StatePublished - May 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Heikamp, E. B., Patel, C. H., Collins, S., Waickman, A., Oh, M. H., Sun, I. H., Illei, P., Sharma, A., Naray-Fejes-Toth, A., Fejes-Toth, G., Misra-Sen, J., Horton, M. R., & Powell, J. D. (2014). The AGC kinase SGK1 regulates T H 1 and T H 2 differentiation downstream of the mTORC2 complex. Nature Immunology, 15(5), 457-464. https://doi.org/10.1038/ni.2867