Phosphorylation of Elk-1 by MEK/ERK pathway is necessary for c-fos gene activation during cardiac myocyte hypertrophy

Cardiac hypertrophy is associated with specific alterations in myocardial g ene expression; however, the exact mechanisms responsible for altered gene expression are poorly defined. The goal of this study was to investigate wh ether signaling kinases that are activated during cardiac hypertrophy direc tly modulate transcription factor activity and regulate gene expression. In an effort to understand this process, we focused our studies on the transc riptional activation of c-fos gene through the serum response element (SRE) /ternary complex factor (TCF) element, during phenylephrine-induced myocyte hypertrophy. In this study, we show that phosphorylated Elk-1, a TCE binds to c-fos SRE and its binding to SRE is increased upon phenylephrine stimul ation. Phenylephrine treatment activates phosphorylation of Elk-1 in the nu cleus within five minutes and Elk-1-dependent transcriptional activation is abolished by inhibitors selective for MEK/ERK kinases. These studies impli cate that phosphorylation of Elk-1 by ERK kinase pathway is important for e arly gene activation during phenylephrine-induced myocyte hypertrophy. (C) 2000 Academic Press.