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Extracellular signal‐regulated kinase 1/2 (ERK1/2) signaling in cardiac hypertrophy
Author(s) -
Kehat Izhak,
Molkentin Jeffery D.
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.05088.x
Subject(s) - pressure overload , muscle hypertrophy , medicine , endocrinology , phosphorylation , stimulation , kinase , phosphatase , signal transduction , genetically modified mouse , stimulus (psychology) , biology , cardiac hypertrophy , transgene , microbiology and biotechnology , biochemistry , psychology , psychotherapist , gene
Cardiac hypertrophy results from increased mechanical load on the heart and through the action of neurohumoral mediators. ERK1/2 are known to be activated in response to almost every stress‐ and agonist‐induced hypertrophic stimulus examined to date, suggesting the straightforward hypothesis that these kinases are required for promoting the cardiac growth response. However, recent data from genetically modified mouse models suggest a more complicated picture. For example, inducible expression of dual‐specificity phosphatase 6, an ERK1/2‐inactivating phosphatase, eliminated ERK1/2 phosphorylation in transgenic mice, but it did not diminish the hypertrophic response to pressure overload. Similarly, Erk1 −/− and Erk2 +/− mice showed no reduction in stimulus‐induced cardiac growth in vivo . However, blockade or deletion of cardiac ERK1/2 did predispose the heart to decompensation and failure after long‐term pressure overload. Thus, ERK1/2 signaling is not to be absolutely necessary for mediating cardiac hypertrophy, although it does appear to provide critical protective effects/signals during stress‐stimulation.