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MAP kinase activation by interleukin-9 in lymphoid and mast cell lines

Abstract

Interleukin-9 (IL-9) stimulates the proliferation of mast cells and lymphocytes. In the present study, we showed that IL-9 induced a transient phosphorylation of MEK, ERK2 and p90/RSK in murine lymphoid and mast cell lines. ERK2 in vitro kinase activity was also increased upon IL-9 stimulation. Similar results were obtained with IL-4, which had not been previously reported to activate these kinases in hematopoietic cells. Analysis of IL-9 receptor mutants showed that activation of the pathway was correlated with proliferation and with phosphorylation of the adaptor protein SHC, but not IRS2 or GAB2. The MEK inhibitor PD98059 reduced the mitogenic response to IL-4 and IL-9. In addition, expression of a dominant-negative RAS variant blocked ERK phosphorylation and significantly decreased Ba/F3 cell growth in the presence of IL-9, but did not affect expression of pim-1, a STAT target gene. In summary, these results indicate that IL-9 can transiently activate the mitogen-activated protein kinase pathway, which contributes to growth stimulation of hematopoietic cell lines.

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Acknowledgements

We thank Luigi Grasso for very helpful discussion, Jacques Van Snick for donation of reagents and Emiel Van Roost for excellent technical assistance. This work was supported in part by the Belgian Federal Service for Scientific, Technical and Cultural Affairs and by the Action de Recherches Concertées, Communauté Française de Belgique, Direction de la Recherche Scientifique. JB Demoulin is a senior research assistant of the Fonds National de la Recherche Scientifique, Belgium.

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Correspondence to Jean-Christophe Renauld.

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Demoulin, JB., Louahed, J., Dumoutier, L. et al. MAP kinase activation by interleukin-9 in lymphoid and mast cell lines. Oncogene 22, 1763–1770 (2003). https://doi.org/10.1038/sj.onc.1206253

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