磷酸化
RAR相关孤儿受体γ
细胞生物学
化学
癌症研究
生物
转录因子
生物化学
基因
作者
Zhiheng He,Fei Wang,Jing Zhang,Subha Sen,Qihua Pang,Sheng‐Wei Luo,Yousang Gwack,Zuoming Sun
出处
期刊:Journal of Immunology
[American Association of Immunologists]
日期:2017-07-01
卷期号:199 (3): 955-964
被引量:23
标识
DOI:10.4049/jimmunol.1700457
摘要
Abstract Transcription factor retinoid acid–related orphan receptor (ROR)γt 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 RORγt activity. Mass spectrometric analysis of immunoprecipitated RORγt 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. IκB kinase (IKK)α binds and phosphorylates RORγt at S376 but not S484. Knockdown of IKKα, dominant-negative IKKα, and RORγt mutants incapable of interacting with IKKα all decrease Th17 differentiation. Furthermore, nonphosophorylatable RORγt mutant (S376A) impairs whereas phosphomimetic mutant (S376E) stimulates Th17 differentiation independent of IKKα. Therefore, IKKα-dependent phosphorylation of S376 stimulated whereas IKKα-independent phosphorylation of S484 inhibited RORγt function in Th17 differentiation.
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