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 transc ription factor Elk-1 at the serum response element (SRE) is dependent on its phosphorylation by MAPK, PD 98059 also suppressed insulin-induc ed Elk-1 transcriptional activity through the SRE. These data show tha t MAPK plays a critical role in both insulin-mediated growth and Elk-1 -dependent induction of c-fos in VSMCs. (C) 1997 Federation of Europea n Biochemical Societies.