A Raf-induced, MEK-independent signaling pathway regulates atrial natriuretic factor gene expression in cardiac muscle cells

The atrial natriuretic factor (ANF) gene is activated in cardiac myocytes b y Ras and its effector Raf. However, MEK, the best-characterized Raf substr ate, cannot efficiently activate ANF suggesting that Raf uses a MEK-indepen dent pathway to activate ANF. By manipulating MEK and Raf activities so tha t they are equally effective at activating ERK, we now demonstrate that Raf activates at least two signaling pathways in cardiac myocytes that regulat e the ANF promoter; the MEK-->ERK pathway inhibits ANF gene expression whil e a Raf-induced, MEK-independent pathway activates expression. This mechani sm may provide increased ability to regulate ANF expression in response to hypertrophic stimuli. (C) 2000 Federation of European Biochemical Societies .