MAP kinase activation by interleukin-9 in lymphoid and mast cell lines.
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.
Demoulin
Jean-Baptiste
JB
Ludwig Institute for Cancer Research, Université de Louvain, Brussels, Belgium.
Louahed
Jamila
J
Dumoutier
Laure
L
Stevens
Monique
M
Renauld
Jean-Christophe
JC
D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004789:Enzyme Activation; D016906:Interleukin-9 / Q000502:physiology*; D008221:Lymphoid Tissue / Q000201:enzymology*; D020935:MAP Kinase Signaling System; D008407:Mast Cells / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests
D016906:Interleukin-9; D020928:Mitogen-Activated Protein Kinases