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Constitutive activation of the MAPK pathway mediates v- fes –induced mitogenesis in murine macrophages

Blood, ISSN: 0006-4971, Vol: 95, Issue: 12, Page: 3959-3963
2000
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  • Citations
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Article Description

Fes is a nonreceptor tyrosine kinase expressed at the highest level in macrophages. We previously showed that the overexpression of c- fes in murine macrophages of the BAC-1.2F5 cell line renders these cells independent of macrophage colony-stimulating factor (MCSF) for survival and proliferation, although no direct relationship could be established between tyrosine-phosphorylated substrates of Fes- and MCSF receptor–dependent signaling and mitogenesis. In this study, we investigated whether the mitogen-activated protein kinase (MAPK) pathway is involved in the growth factor–independent growth of v- fes –overexpressing macrophages. We found a constitutively increased phosphorylation of extracellularly regulated kinase (ERK) in v- fes –overexpressing macrophages as compared with mock-infected cells. This finding was associated with activation of mitogen/extracellular signal–regulated kinase (MEK) and with constitutive localization of ERK in the nucleus. Treatment of v- fes –overexpressing cells with the MEK-specific inhibitor PD98059 markedly reduced cell growth, hyperphosphorylation, and nuclear localization of ERK, indicating that the MAPK pathway mediates the mitogenic effect of v- fes.

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