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Interleukin-3 and granulocyte-macrophage colony-stimulating factor induce
activation of the MAPKAP kinase 2 resulting in in vitro serine
phosphorylation of the small heat shock protein (Hsp 27)
A Ahlers, K Engel, C Sott, M Gaestel, F Herrmann and MA Brach
Max-Delbruck Center for Molecular Medicine, Freie Universitat Berlin,
Universitatsklinikum Rudolf Virchow, Germany.
Interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor
(GM-CSF) have previously been reported to induce rapid phosphorylation of
the mitogen-activated protein (MAP) kinase. However, little is known about
signaling events initiated by both hematopoietins that occur downstream of
the MAP kinase. MAP kinase has been shown to phosphorylate the AP-1
transcription factor and also to activate two kinases designated
insulin-stimulated protein kinase-1 and MAP kinase- activated protein
(MAP-KAP) kinase 2. We show here that IL-3 and GM-CSF induce MAPKAP kinase
2 activity in the human megakaryoblastic leukemia cell line MO7 and
phosphorylate the human small heat shock protein Hsp 27 on serine residues
in vitro. GM-CSF also induced Hsp 27 phosphorylation in neutrophils in a
range similar to that observed in MO7 cells, suggesting that MAPKAP kinase
2-mediated Hsp 27 activation occurs independently of proliferation. Hsp 27
phosphorylation was dose- dependent, occurred as early as 5 minutes after
factor exposure, and was inhibited by the tyrosine kinase inhibitors
genistein and herbimycin A. Furthermore, the protein phosphatase A2
abolished IL-3- and GM-CSF-induced serine phosphorylation of Hsp 27. Taken
together, our findings indicate that tyrosine phosphorylation of MAP kinase
is a prerequisite for serine phosphorylation of Hsp 27, which is mediated
by MAPKAP kinase 2. Hsp 27 has shown activation-dependent translocation
from the cytosolic to the nuclear region and has been linked to the
cellular stress response. However, its precise function is largely unknown.
Our data identify Hsp 27 as a target of the IL-3/GM-CSF stimulation pathway
that involves MAP kinase and MAPKAP kinase 2. In addition, our results
indicate that Hsp 27 may be target of phosphorylation events not only in
the stress response but also in unstressed cells responding to cytokine
stimulation.
Volume 83,
Issue 7,
pp. 1791-1798,
04/01/1994
Copyright © 1994 by The American Society of Hematology
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