Inhibition of MAP kinase blocks insulin-mediated DNA synthesis and transcriptional activation of c-fos by Elk-1 in vascular smooth muscle cells.
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.
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University of California, Los Angeles, School of Medicine 90024, USA.
Graf
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Goetze
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Hsueh
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Law
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D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D016762:Genes, fos / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; C494114:Elk1 protein, rat; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007328:Insulin; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one