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

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

doi:10.1002/eji.201444977

<jats:p>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 T cells. 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 α‐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‐γ from NKT cells. RASAL3‐deficient NKT cells treated with α‐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.</jats:p>

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

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

書誌事項

この論文をさがす

説明

収録刊行物

被引用文献 (6)*注記

参考文献 (32)*注記

関連プロジェクト

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