| First Author | He Z | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 3 | Pages | 955-964 |
| PubMed ID | 28667162 | Mgi Jnum | J:251127 |
| Mgi Id | MGI:6099408 | Doi | 10.4049/jimmunol.1700457 |
| Citation | He Z, et al. (2017) Regulation of Th17 Differentiation by IKKalpha-Dependent and -Independent Phosphorylation of RORgammat. J Immunol 199(3):955-964 |
| abstractText | Transcription factor retinoid acid-related orphan receptor (ROR)gammat transcriptionally regulates the genes required for differentiation of Th17 cells that mediate both protective and pathogenic immunity. However, little is known about the function of posttranslational modifications in the regulation of RORgammat activity. Mass spectrometric analysis of immunoprecipitated RORgammat from Th17 cells identified multiple phosphorylation sites. Systematic mutation analysis of the identified phosphorylation sites found that phosphorylation of S376 enhances whereas phosphorylation of S484 inhibits Th17 differentiation. IkappaB kinase (IKK)alpha binds and phosphorylates RORgammat at S376 but not S484. Knockdown of IKKalpha, dominant-negative IKKalpha, and RORgammat mutants incapable of interacting with IKKalpha all decrease Th17 differentiation. Furthermore, nonphosophorylatable RORgammat mutant (S376A) impairs whereas phosphomimetic mutant (S376E) stimulates Th17 differentiation independent of IKKalpha. Therefore, IKKalpha-dependent phosphorylation of S376 stimulated whereas IKKalpha-independent phosphorylation of S484 inhibited RORgammat function in Th17 differentiation. |
