論文

査読有り
2015年5月

RASAL3, a novel hematopoietic RasGAP protein, regulates the number and functions of NKT cells

EUROPEAN JOURNAL OF IMMUNOLOGY
  • Suguru Saito
  • ,
  • Toshihiko Kawamura
  • ,
  • Masaya Higuchi
  • ,
  • Takahiro Kobayashi
  • ,
  • Manami Yoshita-Takahashi
  • ,
  • Maya Yamazaki
  • ,
  • Manabu Abe
  • ,
  • Kenji Sakimura
  • ,
  • Yasuhiro Kanda
  • ,
  • Hiroki Kawamura
  • ,
  • Shuying Jiang
  • ,
  • Makoto Naito
  • ,
  • Takumi Yoshizaki
  • ,
  • Masahiko Takahashi
  • ,
  • Masahiro Fujii

45
5
開始ページ
1512
終了ページ
1523
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1002/eji.201444977
出版者・発行元
WILEY-BLACKWELL

Ras GTPase-activating proteins negatively regulate the Ras/Erk signaling pathway, thereby playing crucial roles in the proliferation, function, and development of various types of cells. In this study, we identified a novel Ras GTPase-activating proteins protein, RASAL3, which is predominantly expressed in cells of hematopoietic lineages, including NKT, B, and Tcells. We established systemic RASAL3-deficient mice, and the mice exhibited a severe decrease in NKT cells in the liver at 8 weeks of age. The treatment of RASAL3-deficient mice with -GalCer, a specific agonist for NKT cells, induced liver damage, but the level was less severe than that in RASAL3-competent mice, and the attenuated liver damage was accompanied by a reduced production of interleukin-4 and interferon- from NKT cells. RASAL3-deficient NKT cells treated with -GalCer in vitro presented augmented Erk phosphorylation, suggesting that there is dysregulated Ras signaling in the NKT cells of RASAL3-deficient mice. Taken together, these results suggest that RASAL3 plays an important role in the expansion and functions of NKT cells in the liver by negatively regulating Ras/Erk signaling, and might be a therapeutic target for NKT-associated diseases.

Web of Science ® 被引用回数 : 11

リンク情報
DOI
https://doi.org/10.1002/eji.201444977
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25652366
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000354182300023&DestApp=WOS_CPL

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