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

Jennifer A. Oliver, Philip E. Lapinski, Beth A. Lubeck, Jackson S. Turner, Luis F. Parada, Yuan Zhu, Philip D. King

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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 naïve 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.

Original languageEnglish (US)
Pages (from-to)292-302
Number of pages11
JournalMolecular Immunology
Volume55
Issue number3-4
DOIs
StatePublished - Oct 1 2013

Keywords

  • Neurofibromin
  • Ras GTPase-activating proteins
  • Signal transduction
  • T cells

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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    Oliver, J. A., Lapinski, P. E., Lubeck, B. A., Turner, J. S., Parada, L. F., Zhu, Y., & King, P. D. (2013). The Ras GTPase-activating protein neurofibromin 1 promotes the positive selection of thymocytes. Molecular Immunology, 55(3-4), 292-302. https://doi.org/10.1016/j.molimm.2013.03.005