Interleukin-9-induced expression of M-Ras/R-Ras3 oncogene in T-helper clones

Jamila Louahed, Luigi Grasso, Charles De Smet, Emiel Van Roost, Claude Wildmann, Nicholas C. Nicolaides, Roy C. Levitt, Jean Christophe Renauld

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

In an attempt to gain insight into the molecular mechanisms involved in interleukin-9 (IL-9) activities, representational difference analysis (RDA) was used to identify messages that are induced by IL-9 in a murine T-helper- cell clone. One of the isolated genes encodes for the newly described M-Ras or R-Ras3, which is part of the Ras gene superfamily. M-Ras expression was found to be induced by IL-9 but not IL-2 or IL-4 in various murine T-helper- cell clones, and this induction seems to be dependent on the JAK/STAT pathway. Contrasting with the potent upregulation of M-Ras expression, M-Ras was not activated by IL-9 at the level of guanosine triphosphate/guanosine diphosphate (GTP/GDP) binding. However, IL-3 increased GTP binding to M-Ras, suggesting that M-Ras induction might represent a new mechanism of cooperativity between cytokines such as IL-3 and IL-9. Constitutively activated M-Ras mutants induced activation of Elk transcription factor by triggering the MAP kinase pathway and allowed for IL-3-independent proliferation of BaF3 cells. Taken together, these results show that cytokines such as IL-9 can regulate the expression of a member of the RAS family possibly involved in growth-factor signal transduction.

Original languageEnglish (US)
Pages (from-to)1701-1710
Number of pages10
JournalBlood
Volume94
Issue number5
StatePublished - Sep 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Louahed, J., Grasso, L., De Smet, C., Van Roost, E., Wildmann, C., Nicolaides, N. C., Levitt, R. C., & Renauld, J. C. (1999). Interleukin-9-induced expression of M-Ras/R-Ras3 oncogene in T-helper clones. Blood, 94(5), 1701-1710.