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Originally published In Press as doi:10.1074/jbc.M909785199 on May 11, 2000
J. Biol. Chem., Vol. 275, Issue 29, 22550-22557, July 21, 2000
Regulation of Interleukin-1 -induced Platelet-derived Growth
Factor Receptor- Expression in Rat Pulmonary Myofibroblasts by p38
Mitogen-activated Protein Kinase*
Yi-Zhe
Wang,
Ping
Zhang,
Annette B.
Rice, and
James C.
Bonner
From the Laboratory of Pulmonary Pathobiology, NIEHS, National
Institutes of Health,
Research Triangle Park, North Carolina 27709
The potential role of p38 mitogen-activated
protein (MAP) kinase in platelet-derived growth factor receptor-
(PDGF-R ) gene expression was investigated using cultured rat
pulmonary myofibroblasts. p38 MAP kinase was constitutively expressed
in myofibroblasts and activated by interleukin (IL)-1 . A
pyridinylimidazole compound, SB203580, completely inhibited the ability
of p38 MAP kinase activity to phosphorylate PHAS-1 substrate. SB203580
inhibited IL-1 -induced up-regulation of PDGF-R mRNA and
protein in a concentration-dependent manner. Other kinase
inhibitors, including the mitogen-activated protein
kinase/extracellular signal-regulated kinase inhibitor PD98059, did not
block up-regulation of PDGF-R . The IL-1 -induced increase in the
number of 125I-PDGF-AA-binding sites at the cell
surface was reduced >70% by pretreatment with SB203580. Accordingly,
an enhancement of PDGF-AA-stimulated DNA synthesis following IL-1
pretreatment was blocked >70% by SB203580. SB203580 did not affect
IL-1 -induced ERK activation, yet enhanced IL-1 -induced JNK
activation approximately 2-fold. Treatment of cells with SB203580 after
inhibition of transcription by actinomycin D decreased the half-life of
IL-1 -induced PDGF-R mRNA from >4 to ~1.5 h. Moreover,
pretreatment of cells with cycloheximide blocked induction of PDGF-R
mRNA by IL-1 , suggesting that de novo protein
synthesis was required for PDGF-R mRNA stabilization. These data
indicate that p38 MAP kinase regulates PDGF-R expression at the
translational level by signaling the synthesis of an
mRNA-stabilizing protein.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Laboratory of
Pulmonary Pathobiology, NIEHS, P.O. Box 12233, Research Triangle Park,
NC 27709. Tel.: 919-541-0766; Fax: 919-541-4133; E-mail: bonnerj@niehs.nih.gov.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
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