Extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in cardiac hypertrophy

Ann N Y Acad Sci. 2010 Feb;1188:96-102. doi: 10.1111/j.1749-6632.2009.05088.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Cardiomegaly / genetics
  • Cardiomegaly / metabolism*
  • Cardiomegaly / pathology
  • Humans
  • MAP Kinase Signaling System*
  • Mitogen-Activated Protein Kinase 1 / deficiency
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / deficiency
  • Mitogen-Activated Protein Kinase 3 / metabolism*

Substances

  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3