Abstract
Insulin-stimulated DNA synthesis, MAP kinase (MAPK) activity and c-fos expression in vascular smooth muscle cells (VSMCs) was blocked by the MAPK inhibitor PD 98059. Regulation of c-fos expression by the transcription factor Elk-1 at the serum response element (SRE) is dependent on its phosphorylation by MAPK. PD 98059 also suppressed insulin-induced Elk-1 transcriptional activity through the SRE. These data show that MAPK plays a critical role in both insulin-mediated growth and Elk-1-dependent induction of c-fos in VSMCs.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Aorta, Thoracic / cytology
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Aorta, Thoracic / drug effects
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Aorta, Thoracic / metabolism*
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cells, Cultured
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DNA-Binding Proteins*
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Enzyme Activation
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology
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Genes, fos / drug effects
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Insulin / pharmacology*
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Muscle, Smooth, Vascular / cytology
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism*
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-fos / biosynthesis*
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RNA, Messenger / biosynthesis
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Rats
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Rats, Sprague-Dawley
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Transcription Factors / metabolism
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Transcription, Genetic / drug effects
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Transcriptional Activation / drug effects
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Transcriptional Activation / physiology*
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ets-Domain Protein Elk-1
Substances
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DNA-Binding Proteins
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Elk1 protein, rat
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Enzyme Inhibitors
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Flavonoids
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Insulin
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-fos
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RNA, Messenger
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Transcription Factors
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ets-Domain Protein Elk-1
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Calcium-Calmodulin-Dependent Protein Kinases
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one