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Rapid activation of proteins that interact with the interferon gamma
activation site in response to multiple cytokines
P Lamb, LV Kessler, C Suto, DE Levy, HM Seidel, RB Stein and J Rosen
Ligand Pharmaceuticals, San Diego, CA 92121.
Many cytokines and growth factors trigger rapid changes in gene expression
upon binding to their receptors. In many cases, the mechanism by which
these changes are affected is unknown. In this report, we show that
interleukin-2 (IL-2), IL-3, IL-4, IL-6, leukemia inhibitory factor (LIF),
erythropoietin (Epo), and granulocyte- macrophage colony-stimulating factor
(GM-CSF) treatment of cells causes rapid activation of DNA-binding
activities that recognize a DNA sequence element previously implicated in
regulation of gene expression by interferon gamma (IFN gamma). The IL-4-,
IL-6-, and GM-CSF-induced complexes can be distinguished from the recently
characterized IFN gamma-activated protein p91 on the basis of mobility in
polyacrylamide gels, sequence preferences, and lack of reactivity with an
anti-p91 antiserum. The IL-4- and GM-CSF-induced complexes react with
antiphosphotyrosine antibodies, demonstrating the presence of
phosphotyrosine-containing proteins in these DNA-binding complexes.
Transcriptional activation of a reporter gene linked to a synthetic IFN
gamma-responsive promoter is observed in response to IFN gamma, IL-6, and
LIF. These data suggest a pathway by which cytokines induce rapid changes
in gene expression.
Volume 83,
Issue 8,
pp. 2063-2071,
04/15/1994
Copyright © 1994 by The American Society of Hematology

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