Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 3959-3963
Constitutive activation of the MAPK pathway mediates
v-fes-induced mitogenesis in murine macrophages
Elisabetta Rovida,
Fabio Marra,
Manuela Baccarini, and
Persio Dello Sbarba
From the Department of Experimental Pathology and Oncology and
Department of Internal Medicine, Università degli Studi di
Firenze, Florence, Italy; and the Institute for Microbiology and
Genetics, Universität Wien, Vienna, Austria.
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.
