Lymphoproliferative defects in mice lacking the expression of neurofibromin

Functional and biochemical consequences of Nf1 deficiency in T-cell development and function

David Ingram, Lei Zhang, Jennifer McCarthy, Mary Jo Wenning, Lucy Fisher, Feng Chun Yang, D. Clapp, Reuben Kapur

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3656-3662
Number of pages7
JournalBlood
Volume100
Issue number10
DOIs
StatePublished - Nov 15 2002

Fingerprint

Neurofibromin 1
T-cells
T-Lymphocytes
Defects
ras GTPase-Activating Proteins
Lymphocytes
Thymus Hyperplasia
Guanosine
Interleukin-2 Receptors
T-Lymphocyte Subsets
Thymocytes
T-Cell Antigen Receptor
Tumor Suppressor Genes
Thymidine
Homeostasis
Tumors
Proteins
Genes
Chemical activation

ASJC Scopus subject areas

  • Hematology

Cite this

Lymphoproliferative defects in mice lacking the expression of neurofibromin : Functional and biochemical consequences of Nf1 deficiency in T-cell development and function. / Ingram, David; Zhang, Lei; McCarthy, Jennifer; Wenning, Mary Jo; Fisher, Lucy; Yang, Feng Chun; Clapp, D.; Kapur, Reuben.

In: Blood, Vol. 100, No. 10, 15.11.2002, p. 3656-3662.

Research output: Contribution to journalArticle

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