| First Author | Saito S | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 5 | Pages | 1512-23 |
| PubMed ID | 25652366 | Mgi Jnum | J:229641 |
| Mgi Id | MGI:5752714 | Doi | 10.1002/eji.201444977 |
| Citation | Saito S, et al. (2015) RASAL3, a novel hematopoietic RasGAP protein, regulates the number and functions of NKT cells. Eur J Immunol 45(5):1512-23 |
| abstractText | 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 alpha-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-gamma from NKT cells. RASAL3-deficient NKT cells treated with alpha-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. |
