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.