Activated Rho A Stimulates c- fos Gene Expression in Myocardial Cells

Abstract

Abstract Rho regulates various cell functions, including cell morphology and motility. However, the functional role of Rho on the signaling pathway in myocardial cells (MCs) is unknown. In the present study, we attempted to explore the mode of Rho action for c- fos gene expression in MCs. Expression of the c- fos promoter/enhancer linked to the luciferase reporter gene (c- fos luciferase) was stimulated by the wild type of Rho A and the point-mutated active form of Rho A ( Rho A Val14) but not the biologically inactive effector domain mutant of Rho A. Rho GDP dissociation inhibitor inhibited the action of Rho A on c- fos luciferase expression. The deletion analysis revealed that the c- fos serum response element (SRE) and the 12- O -tetradecanoylphorbol-13-acetate response element (TRE) mainly account for c- fos luciferase expression by Rho A Val14. The c- fos SRE mutant, which contains an intact binding site for the serum response factor but lacks the ternary complex factor binding site, was activated by Rho A Val14. The action of Rho A Val14 on c- fos luciferase expression was not inhibited by downregulation of protein kinase C, protein kinase C inhibitors, or tyrosine kinase inhibitors. These results indicate that activated Rho A stimulates c- fos gene expression through the c- fos SRE and TRE and that the signaling pathway from activated Rho A to the c- fos promoter/enhancer is independent of these inhibitor-sensitive pathways in MCs.