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Blood, Vol. 92 No. 4 (August 15), 1998:
pp. 1142-1149
RAPID COMMUNICATION
Synergistic Activation of MAP Kinase (ERK1/2) by Erythropoietin and
Stem Cell Factor Is Essential for Expanded Erythropoiesis
Xingwei Sui,
Sanford B. Krantz,
Min You, and
Zhizhuang Zhao
From the Hematology Division, Department of Medicine, Department of
Veterans Affairs Medical Center, and Vanderbilt Cancer Center,
Vanderbilt University, Nashville, TN.
Stem cell factor (SCF) and erythropoietin (EPO) work synergistically
to support erythropoiesis, but the mechanism for this synergism is
unknown. By using purified human erythroid colony-forming cells (ECFC),
we have found that SCF and EPO synergistically activate MAP kinase
(MAPK, ERK1/2), which correlates with the cell growth and thus may be
responsible for the synergistic effects. Treatment of the cells with
PD98059 and wortmannin, inhibitors of MEK and PI-3 kinase,
respectively, inhibited the synergistic activation of MAPK and also the
cell growth, further supporting this conclusion. Wortmannin only
inhibits MAPK activation induced by EPO but not that by SCF, suggesting
that SCF and EPO may activate MAPK through different pathways, which
would facilitate synergy. Furthermore, EPO, but not SCF, led to
activation of STAT5, whereas SCF and wortmannin had no effect on the
EPO-induced STAT5 activation, suggesting that STAT5 is not involved in
the synergistic action of SCF and EPO. Together, the data suggest that
synergistic activation of MAPK by SCF and EPO is essential for expanded
erythropoiesis.
© 1998 by The American Society of Hematology.
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