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TGF-ß-induced phosphorylation of Akt and Foxo transcription factors negatively regulates induced regulatory T cell differentiation.
Kurebayashi, Yutaka; Baba, Yukiko; Minowa, Akiko; Nadya, Niken Adiba; Azuma, Miyuki; Yoshimura, Akihiko; Koyasu, Shigeo; Nagai, Shigenori.
Afiliação
  • Kurebayashi Y; Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan; Department of Pathology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
  • Baba Y; Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
  • Minowa A; Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
  • Nadya NA; Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8549, Japan.
  • Azuma M; Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8549, Japan.
  • Yoshimura A; Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology (JST), Tokyo 102-0075, Japan.
  • Koyasu S; Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan; Laboratory for Immune Cell System, RCAI, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Kanagawa 230-0045, Japan.
  • Nagai S; Department of Microbiology and Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan; Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8549, Japan. Electronic address: nagai.mim@
Biochem Biophys Res Commun ; 480(1): 114-119, 2016 Nov 04.
Article em En | MEDLINE | ID: mdl-27697523
Transforming growth factor-ß (TGF-ß) is a pivotal cytokine in the differentiation of regulatory T cells, and Foxo transcription factors positively regulate this process. On the other hand, the function of Foxo transcription factors is negatively regulated by PI3K/Akt signaling, which is activated by TGF-ß in many types of cells; yet the role of TGF-ß in Akt activity and its downstream substrates in CD4+ T cells, including Foxo transcription factors, remains to be determined. Herein, we demonstrate that TGF-ß selectively induces Akt phosphorylation at Ser473 but not at Thr308 in a class IA PI3K-dependent manner in CD4+ T cells, resulting in the phosphorylation and inhibition of Foxo transcription factors and negatively regulating the differentiation of induced regulatory T cells (iTregs). These observations reveal a novel negative regulatory mechanism involving Akt and Foxo transcription factors induced by TGF-ß in the iTreg differentiation process.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fator de Crescimento Transformador beta / Linfócitos T Reguladores / Proteínas Proto-Oncogênicas c-akt / Proteína Forkhead Box O1 Limite: Animals Idioma: En Revista: Biochem Biophys Res Commun Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fator de Crescimento Transformador beta / Linfócitos T Reguladores / Proteínas Proto-Oncogênicas c-akt / Proteína Forkhead Box O1 Limite: Animals Idioma: En Revista: Biochem Biophys Res Commun Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Japão