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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References
Crowley M, Harmer S and DeFranco A . (1996). J. Biol. Chem., 271, 1145–1152.
Demoulin JB, Grasso L, Atkin JM, Stevens M, Louahed J, Levitt RC, Nicolaides NC and Renauld J . (2000a). FEBS Lett., 482, 200–204.
Demoulin JB, Uyttenhove C, Lejeune D, Mui A, Groner B and Renauld JC . (2000b). Cancer Res., 15, 3971–3977.
Demoulin JB and Renauld JC . (1998). Cytokines Cell. Mol. Ther., 4, 243–256.
Demoulin JB, Uyttenhove C, Van Roost E, de Lestre B, Donckers D, Van Snick J and Renauld JC . (1996). Mol. Cell Biol., 16, 4710–4716.
Demoulin JB, Van Roost E, Stevens M, Groner B and Renauld JC . (1999). J. Biol. Chem., 274, 25855–25861.
Demoulin JB, Van Snick J and Renauld JC . (2001). Cell Growth Differ., 12, 169–174.
de Rooij J and Bos J . (1997). Oncogene, 14, 623–625.
Duronio V, Welham M, Abraham S, Dryden P and Schrader J . (1992). Proc. Natl. Acad. Sci. USA, 89, 1587–1591.
Frodin M and Gammeltoft S . (1999). Mol. Cell. Endocrinol., 1999, 65–77.
Gadina M, Sudarshan C, Visconti R, Zhou YJ, Gu H, Neel BG and O'Shea JJ . (2000). J. Biol. Chem., 275, 26959–26966.
Gingras S, Cote S and Simard J . (2000). Mol. Endocrinol., 147, 229–240.
Gomez J, Martinez C, Fernandez B, Garcia A and Rebollo A . (1996). J. Immunol., 157, 2272–2281.
Gu H, Pratt JC, Burakoff SJ and Neel BG . (1998). Mol. Cell, 2, 729–740.
Kaplan MH, Schindler U, Smiley ST and Grusby MJ . (1996). Immunity, 4, 313–319.
Keegan AD, Nelms K, White M, Wang LM, Pierce JH and Paul WE . (1994). Cell, 76, 811–820.
Lemoli RM, Fortuna A, Tafuri A, Fogli M, Amabile M, Grande A, Ricciardi MR, Petrucci MT, Bonsi L, Bagnara G, Visani G, Martinelli G, Ferrari S and Tura S . (1996). Blood, 87, 3852–3859.
Louahed J, Grasso L, De Smet C, Van Roost E, Wildmann C, Nicolaides NC, Levitt RC and Renauld JC . (1999). Blood, 94, 1701–1710.
Louahed J, Zhou Y, Maloy WL, Rani PU, Weiss C, Tomer Y, Vink A, Renauld JC, Van Snick J, Nicolaides NC, Levitt RC and Haczku A . (2001). Blood, 97, 1035–1042.
Miyata Y and Nishida E . (1999). Biochem. Biophys. Res. Commun., 266, 291–295.
Miyazawa K, Hendrie PC, Kim YJ, Mantel C, Yang YC, Kwon BS and Broxmeyer HE . (1992). Blood, 80, 1685–1692.
Murphy LO, Smith S, Chen RH, Fingar DC and Blenis J . (2002). Molecular interpretation of ERK signal duratiion byy immediate early gene products. Nat. Cell Biol., 4, 556–564.
Nelms K, Keegan AD, Zamorano J, Ryan JJ and Paul WE . (1999). Annu. Rev. Immunol., 17, 701–738.
Nicolaides NC, Holroyd KJ, Ewart SL, Eleff SM, Kiser MB, Dragwa CR, Sullivan CD, Grasso L, Zhang LY, Messler CJ, Zhou T, Kleeberger SR, Buetow KH and Levitt RC . (1997). Proc. Natl. Acad. Sci. USA, 94, 13175–13180.
Nosaka T, Kawashima T, Misawa K, Ikuta K, Mui AL and Kitamura T . (1999). EMBO J., 18, 4754–4765.
Pruett W, Yuan Y, Rose E, Batzer AG, Harada N and Skolnik E . (1995). Mol. Cell. Biol., 15, 1778–1785.
Renauld JC, Kermouni A, Vink A, Louahed J and Van Snick J . (1995). J. Leuk. Biol., 57, 353–360.
Renauld JC, van der Lugt N, Vink A, van Roon M, Godfraind C, Warnier G, Merz H, Feller A, Berns A and Van Snick J . (1994). Oncogene, 9, 1327–1332.
Renauld J-C and Van Snick J . (1998). The Cytokine Handbook. Thomson A (ed). Academic Press: New York, pp. 313–331.
Richard M, Grencis RK, Humphreys NE, Renauld JC and, Van Snick J . (2000). Proc. Natl. Acad. Sci. USA, 97, 767–772.
Robinson M and Cobb M . (1997). Curr. Opin. Cell Biol., 9, 180–186.
Rohrschneider L, Fuller J, Wolf I, Liu Y and Lucas D . (2000). Genes Dev., 14, 505–520.
Rolling C, Treton D, Pellegrini S, Galanaud P and Richard Y . (1996). FEBS Lett., 393, 53–56.
Satoh T, Nakafuku M, Miyajima A and Kaziro Y . (1991). Proc. Natl. Acad. Sci. USA, 88, 3314–3318.
Temann UA, Geba GP, Rankin JA and Flavell RA . (1998). J. Exp. Med., 188, 1307–1320.
Terada K, Kaziro Y and Satoh T . (1995). J. Biol. Chem., 270, 27880–27886.
Vink A, Warnier G, Brombacher F and Renauld JC . (1999). J. Exp. Med., 189, 1413–1423.
Welham M, Duronio V and Schrader J . (1994). J. Biol. Chem., 269, 5865–5873.
Welham M, Learmonth L, Bone H and Schrader J . (1995). J. Biol. Chem., 270, 12286–12296.
Xiao H, Yin T, Wang XY, Uchida T, Chung J, White MF and Yang YC . (2002). J. Biol. Chem., 277, 8091–8098.
Yin T, Keller SR, Quelle FW, Witthuhn BA, Tsang ML, Lienhard GE, Ihle JN and Yang YC . (1995). J. Biol. Chem., 270, 20497–20502.
Zamorano J and Keegan A . (1998). J. Immunol., 161, 859–867.
Zhu YX, Sun HB, Tsang ML, McMahel J, Grigsby S, Yin T and Yang YC . (1997). J. Biol. Chem., 272, 21334–21340.
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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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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DOI: https://doi.org/10.1038/sj.onc.1206253