The AGC kinase SGK1 regulates TH1 and TH2 differentiation downstream of the mTORC2 complex View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-05

AUTHORS

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

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. More... »

PAGES

457-464

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ni.2867

DOI

http://dx.doi.org/10.1038/ni.2867

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1029984030

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24705297


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