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Phosphorylation status determines the opposing functions of Smad2/Smad3 as STAT3 cofactors in T(H)17 differentiation
- Title
- Phosphorylation status determines the opposing functions of Smad2/Smad3 as STAT3 cofactors in T(H)17 differentiation
- Authors
- Yoon, Jeong-Hwan; Sudo, Katsuko; Kuroda, Masahiko; Kato, Mitsuyasu; Lee, In-Kyu; Han, Jin Soo; Nakae, Susumu; Imamura, Takeshi; Kim, Juryun; Ju, Ji Hyeon; Kim, Dae-Kee; Matsuzaki, Koichi; Weinstein, Michael; Matsumoto, Isao; Sumida, Takayuki; Mamura, Mizuko
- Ewha Authors
- 김대기
- SCOPUS Author ID
- 김대기
- Issue Date
- 2015
- Journal Title
- NATURE COMMUNICATIONS
- ISSN
- 2041-1723
- Citation
- NATURE COMMUNICATIONS vol. 6
- Publisher
- NATURE PUBLISHING GROUP
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Transforming growth factor-beta (TGF-beta) and interleukin-6 (IL-6) are the pivotal cytokines to induce IL-17-producing CD4(+) T helper cells (T(H)17); yet their signalling network remains largely unknown. Here we show that the highly homologous TGF-beta receptor-regulated Smads (R-Smads): Smad2 and Smad3 oppositely modify STAT3-induced transcription of IL-17A and retinoic acid receptor-related orphan nuclear receptor, ROR gamma t encoded by Rorc, by acting as a co-activator and co-repressor of STAT3, respectively. Smad2 linker phosphorylated by extracellular signal-regulated kinase (ERK) at the serine 255 residue interacts with STAT3 and p300 to transactivate, whereas carboxy-terminal unphosphorylated Smad3 interacts with STAT3 and protein inhibitor of activated STAT3 (PIAS3) to repress the Rorc and Il17a genes. Our work uncovers carboxy-terminal phosphorylation-independent noncanonical R-Smad-STAT3 signalling network in T(H)17 differentiation.
- DOI
- 10.1038/ncomms8600
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
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