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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-03-0734. This Article Full Text (PDF) All Versions of this Article: 2002-03-0734v1 100/10/3656    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ingram, D. A Articles by Kapur, R. Search for Related Content PubMed PubMed Citation Articles by Ingram, D. A Articles by Kapur, R. Social Bookmarking                   What's this? Submitted March 8, 2002 Accepted June 3, 2002 Lymphoproliferative Defects in Mice Lacking the Expression of Neurofibromin: Functional and Biochemical Consequences of Nf1 Deficiency in T Cell Development and Function David A Ingram, Lei Zhang, Jennifer McCarthy, Mary Jo Wenning, Lucy Fisher, Feng-Chun Yang, D W Clapp, and Reuben Kapur* Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, IN, USA * Corresponding author; email: rkapur{at}iupui.edu. Ras plays an essential role in lymphocyte development and function. However, in vivo consequences(s) of regulation of Ras activity by GTPase activating proteins (GAPs) on lymphocyte development and function are not known. In this study we demonstrate that neurofibromin, the protein encoded by the NF1 tumor suppressor gene functions as a GAP for Ras in T cells. Loss of Nf1 in T cells results in enhanced Ras activation, which is associated with thymic and splenic hyperplasia, and an increase in the absolute number of immature and mature T cell subsets compared to control mice. Interestingly, in spite of a profound T cell expansion and higher thymidine incorporation in unstimulated Nf1-deficient T cells, T cell receptor and interleukin-2 receptor mediated proliferation of thymocytes and mature T cells was significantly reduced compared to control mice. Collectively, these results identify neurofibromin as a GAP for Ras in T cells for maintaining immune homeostasis in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Guo, J. A. Cancelas, D. Hildeman, D. A. Williams, and Y. Zheng Rac GTPase isoforms Rac1 and Rac2 play a redundant and crucial role in T-cell development Blood, September 1, 2008; 112(5): 1767 - 1775. [Abstract] [Full Text] [PDF] H. Chen, Y. Qiu, L. Chen, L. Li, J. Chen, C. Zhang, B. Wang, Y. Yu, Z. Zhu, F. Zhu, et al. The Expression of Neurofibromin in Human Osteoblasts and Chondrocytes Ann. Clin. Lab. Sci., January 1, 2008; 38(1): 25 - 30. [Abstract] [Full Text] [PDF] G. Yang, W. Khalaf, L. van de Locht, J. H. Jansen, M. Gao, M. A. Thompson, B. A. van der Reijden, D. H. Gutmann, R. Delwel, D. W. Clapp, et al. Transcriptional Repression of the Neurofibromatosis-1 Tumor Suppressor by the t(8;21) Fusion Protein Mol. Cell. Biol., July 15, 2005; 25(14): 5869 - 5879. [Abstract] [Full Text] [PDF] D. T. Le, N. Kong, Y. Zhu, J. O. Lauchle, A. Aiyigari, B. S. Braun, E. Wang, S. C. Kogan, M. M. Le Beau, L. Parada, et al. Somatic inactivation of Nf1 in hematopoietic cells results in a progressive myeloproliferative disorder Blood, June 1, 2004; 103(11): 4243 - 4250. [Abstract] [Full Text] [PDF]

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