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Characterization of cis-acting sequences and trans-acting signals
regulating early growth response 1 and c-fos promoters through the
granulocyte-macrophage colony-stimulating factor receptor in BA/F3 cells
S Watanabe, H Kubota, KM Sakamoto and K Arai
Department of Molecular and Developmental Biology, Institute of Medical
Science, The University of Tokyo, Japan.
Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) activates
a set of genes such as c-fos, jun, myc, and early growth response gene 1
(egr-1). Studies on BA/F3 cells that express hGM-CSF receptor (hGMR) showed
that two different signaling pathways controlled by distinct regions within
the beta subunit are involved in activation of c-fos/c-jun genes and in
c-myc, respectively. However, the region(s) of the beta subunit responsible
for activation of the egr-1 gene and other regulatory genes has not been
identified. We describe here how egr-1 promoter is activated by hGMR
through two regions of the beta subunit, with these regions being required
for activation of the c-fos promoter. Coexpression of dominant negative
(dn) Ras (N17ras) or dn JAK2 almost completely suppressed the activation of
egr-1 and c-fos promoters. Deletion analysis of egr-1 promoter showed two
cis-acting regions responsible for activation by hGM-CSF or mouse
interleukin-3 (mIL-3), one between nucleotide positions (nt) -56 and -116,
and the other between nt -235 and -480, which contains tandem repeats of
the serum response element (SRE) sites. Similar experiments with the c-fos
promoter showed that cis-acting regions containing the SRE/AP-1 sites is
sufficient for activation by hGM-CSF. Based on these observations, we
propose that signaling pathways activating egr-1 and c-fos promoters are
controlled by SRE elements, either through the same or overlapping pathways
that involve JAK2 and Ras.
Volume 89,
Issue 4,
pp. 1197-1206,
02/15/1997
Copyright © 1997 by The American Society of Hematology
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