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Publication : The Ras GTPase-activating protein neurofibromin 1 promotes the positive selection of thymocytes.

First Author  Oliver JA Year  2013
Journal  Mol Immunol Volume  55
Issue  3-4 Pages  292-302
PubMed ID  23522726 Mgi Jnum  J:202145
Mgi Id  MGI:5517537 Doi  10.1016/j.molimm.2013.03.005
Citation  Oliver JA, et al. (2013) The Ras GTPase-activating protein neurofibromin 1 promotes the positive selection of thymocytes. Mol Immunol 55(3-4):292-302
abstractText  TCR-mediated activation of the Ras signaling pathway is critical for T cell development in the thymus and function in the periphery. However, which members of a family of Ras GTPase-activating proteins (RasGAPs) negatively regulate Ras activation in T cells is unknown. In this study we examined a potential function for the neurofibromin 1 (NF1) RasGAP in the T cell lineage with the use of T cell-specific NF1-deficient mice. Surprisingly, on an MHC class I-restricted TCR transgenic background, NF1 was found to promote thymocyte positive selection. By contrast, NF1 neither promoted nor inhibited the negative selection of thymocytes. In the periphery, NF1 was found to be necessary for the maintenance of normal numbers of naive CD4(+) and CD8(+) T cells but was dispensable as a regulator of TCR-induced Ras activation, cytokine synthesis, proliferation and differentiation and death. These findings point to a novel unexpected role for NF1 in T cell development as well as a regulator of T cell homeostasis.
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