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Overexpression of mitogen-activated protein kinase (ERK1) enhances T- cell
cytokine gene expression: role of AP1, NF-AT, and NF-KB
JH Park and L Levitt
Department of Medicine, Stanford University Medical Center, CA 94305.
Transfected Jurkat cells overexpressing extracellular signal-regulated
kinase (ERK1), also referred to as mitogen-activated protein (MAP) kinase,
were selected by Western blotting assay using anti-ERK1 and
antiphosphotyrosine antibodies in combination with a functional MAP kinase
assay. We then asked whether enhanced ERK1 expression had any effect on
induction of T-cell cytokine genes. The results show that overexpression of
ERK1 enhances expression of T-cell interleukin-2 (IL- 2), IL-3, and
granulocyte-macrophage colony-stimulating factor mRNA; no change was seen
in expression of the alpha-actin gene. DNA-binding activities of the
transcription factors AP1, NF-AT, and NF-kB were specifically increased
twofold to fourfold in ERK1-overexpressing clones relative to
nontransformed or vector-transformed cells, whereas no enhancement of
CK1-CK2 protein DNA binding activity was detected after ERK1
overexpression. Additionally, increased NF-AT DNA binding activity was
associated with functional enhancement of NF-AT transactivating activity in
ERK1-overexpressing cells. These results provide direct evidence for the
role of MAP kinase in the regulation of cytokine gene expression and
indicate that such regulation is likely mediated through the enhanced DNA
binding activity of specific nuclear transcription factors.
Volume 82,
Issue 8,
pp. 2470-2477,
10/15/1993
Copyright © 1993 by The American Society of Hematology
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