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

Emily B. Heikamp, Chirag H. Patel, Samuel Lester Collins, Adam Waickman, Min Hee Oh, Im Hong Sun, Peter B Illei, Archna Sharma, Aniko Naray-Fejes-Toth, Geza Fejes-Toth, Jyoti Misra-Sen, Maureen Horton, Jonathan 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 - 2014

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Phosphotransferases
Interferons
T Cell Transcription Factor 1
T-Lymphocytes
Ubiquitin-Protein Ligases
Sodium Channels
Virus Diseases
Ion Channels
Protein Isoforms
Transcription Factors
Asthma
Kidney
TOR complex 2
Neoplasms

ASJC Scopus subject areas

  • Immunology

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The AGC kinase SGK1 regulates T H 1 and T H 2 differentiation downstream of the mTORC2 complex. / Heikamp, Emily B.; Patel, Chirag H.; Collins, Samuel Lester; Waickman, Adam; Oh, Min Hee; Sun, Im Hong; Illei, Peter B; Sharma, Archna; Naray-Fejes-Toth, Aniko; Fejes-Toth, Geza; Misra-Sen, Jyoti; Horton, Maureen; Powell, Jonathan.

In: Nature Immunology, Vol. 15, No. 5, 2014, p. 457-464.

Research output: Contribution to journalArticle

Heikamp, EB, Patel, CH, Collins, SL, Waickman, A, Oh, MH, Sun, IH, Illei, PB, Sharma, A, Naray-Fejes-Toth, A, Fejes-Toth, G, Misra-Sen, J, Horton, M & Powell, J 2014, 'The AGC kinase SGK1 regulates T H 1 and T H 2 differentiation downstream of the mTORC2 complex', Nature Immunology, vol. 15, no. 5, pp. 457-464. https://doi.org/10.1038/ni.2867
Heikamp, Emily B. ; Patel, Chirag H. ; Collins, Samuel Lester ; Waickman, Adam ; Oh, Min Hee ; Sun, Im Hong ; Illei, Peter B ; Sharma, Archna ; Naray-Fejes-Toth, Aniko ; Fejes-Toth, Geza ; Misra-Sen, Jyoti ; Horton, Maureen ; Powell, Jonathan. / The AGC kinase SGK1 regulates T H 1 and T H 2 differentiation downstream of the mTORC2 complex. In: Nature Immunology. 2014 ; Vol. 15, No. 5. pp. 457-464.
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