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A Raf‐induced, MEK‐independent signaling pathway regulates atrial natriuretic factor gene expression in cardiac muscle cells
Author(s) -
Jette Cicely,
Thorburn Andrew
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01114-5
Subject(s) - mapk/erk pathway , effector , mek inhibitor , signal transduction , myocyte , microbiology and biotechnology , chemistry , medicine , gene expression , endocrinology , cardiac myocyte , gene , biology , biochemistry
The atrial natriuretic factor (ANF) gene is activated in cardiac myocytes by Ras and its effector Raf. However, MEK, the best‐characterized Raf substrate, cannot efficiently activate ANF suggesting that Raf uses a MEK‐independent pathway to activate ANF. By manipulating MEK and Raf activities so that they are equally effective at activating ERK, we now demonstrate that Raf activates at least two signaling pathways in cardiac myocytes that regulate the ANF promoter; the MEK→ERK pathway inhibits ANF gene expression while a Raf‐induced, MEK‐independent pathway activates expression. This mechanism may provide increased ability to regulate ANF expression in response to hypertrophic stimuli.