Extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in cardiac hypertrophy.
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.
Kehat
Izhak
I
Department of Pediatrics, University of Cincinnati, Cincinnati Children's Hospital Medical Center, and the Howard Hughes Medical Institute, Cincinnati, Ohio 45229-3039, USA. izhak.kehat@cchmc.org
Molkentin
Jeffery D
JD
D000818:Animals; D017209:Apoptosis; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000172:deficiency / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000172:deficiency / Q000378:metabolism*
D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3