MTORC1 Promotes T-bet Phosphorylation To Regulate Th1 Differentiation.

ABSTRACT: CD4⁺ T cells lacking the mTORC1 activator Rheb fail to secrete IFN-γ under Th1 polarizing conditions. We hypothesized that this phenotype is due to defects in regulation of the canonical Th1 transcription factor T-bet at the level of protein phosphorylation downstream of mTORC1. To test this hypothesis, we employed targeted mass-spectrometry proteomic analysis-multiple reaction monitoring mass spectrometry. We used this method to detect and quantify predicted phosphopeptides derived from T-bet. By analyzing activated murine wild-type and Rheb-deficient CD4⁺ T cells, as well as murine CD4⁺ T cells activated in the presence of rapamycin, a pharmacologic inhibitor of mTORC1, we were able to identify six T-bet phosphorylation sites. Five of these are novel, and

SUBMITTER: Chornoguz O 

PROVIDER: S-EPMC5458608 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature