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

In an attempt to gain insight into the molecular mechanisms involved in int erleukin-9 (IL-9) activities, representational difference analysis (RDA) wa s used to identify messages that are induced by IL-9 in a murine T-helper-c ell 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 path way. Contrasting with the potent upregulation of M-Ras expression, M-Ras wa s not activated by IL-9 at the level of guanosine triphosphate/guanosine di phosphate (GTP/GDP) binding. However, IL-3 increased GTP binding to M-Ras, suggesting that M-Ras induction might represent a new mechanism of cooperat ivity between cytokines such as IL-3 and IL-9, Constitutively activated M-R as 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 r egulate the expression of a member of the RAS family possibly involved in g rowth-factor signal transduction. (C) 1999 by The American Society of Hemat ology.