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

Louahed, Jamila;Grasso, Luigi;De Smet, Charles;Van Roost, Emiel;Renauld, Jean-Christophe;et.al.
(1999) Blood — Vol. 94, n° 5, p. 1701-1710 (1999)

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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 Pas 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. (C) 1999 by The American Society of Hematology.
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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. https://doi.org/10.1182/blood.V94.5.1701 (Original work published 1999)