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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 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 Citation Map 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. Related Collections Hematopoiesis and Stem Cells Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 November 2002, Vol. 100, No. 10, pp. 3656-3662 IMMUNOBIOLOGY 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. Wade Clapp, and Reuben Kapur From the Section of Neonatal-Perinatal Medicine, Department of Pediatrics, Herman B. Wells Center for Pediatric Research and the Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN. Ras plays an essential role in lymphocyte development and function. However, in vivo consequence(s) of regulation of Ras activity by guanosine triphosphatase (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 with 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 substantially reduced compared with control mice. Collectively, these results identify neurofibromin as a GAP for Ras in T cells for maintaining immune homeostasis in vivo. © 2002 by The American Society of Hematology.   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]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020