Publication Date:
2015-02-05
Description:
Ras GTPase-activating proteins (RasGAPs) 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 RasGAP 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 natural killer T (NKT) cells in the liver at eight 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. This article is protected by copyright. All rights reserved
Print ISSN:
0014-2980
Electronic ISSN:
1521-4141
Topics:
Medicine