The eIF2B-interacting domain of RGS2 protects against GPCR agonist-induced hypertrophy in neonatal rat cardiomyocytes

Cell Signal. 2014 Jun;26(6):1226-34. doi: 10.1016/j.cellsig.2014.02.006. Epub 2014 Feb 24.


The protective effect of Regulator of G protein Signaling 2 (RGS2) in cardiac hypertrophy is thought to occur through its ability to inhibit the chronic GPCR signaling that promotes pathogenic growth both in vivo and in cultured cardiomyocytes. However, RGS2 is known to have additional functions beyond its activity as a GTPase accelerating protein, such as the ability to bind to eukaryotic initiation factor, eIF2B, and inhibit protein synthesis. The RGS2 eIF2B-interacting domain (RGS2(eb)) was examined for its ability to regulate hypertrophy in neonatal ventricular myocytes. Both full-length RGS2 and RGS2(eb) were able to inhibit agonist-induced cardiomyocyte hypertrophy, but RGS2(eb) had no effect on receptor-mediated inositol phosphate production, cAMP production, or ERK 1/2 activation. These results suggest that the protective effects of RGS2 in cardiac hypertrophy may derive at least in part from its ability to govern protein synthesis.

Keywords: Cardiac hypertrophy; G protein; GPCR; Protein synthesis; RGS protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cardiomegaly / metabolism*
  • Cell Size / drug effects
  • Cells, Cultured
  • Cyclic AMP / metabolism
  • Eukaryotic Initiation Factor-2B
  • Gene Expression
  • Inositol Phosphates / metabolism
  • Isoproterenol / pharmacology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Phenylephrine / pharmacology
  • Protein Biosynthesis
  • Protein Interaction Domains and Motifs
  • RGS Proteins / chemistry
  • RGS Proteins / physiology*
  • Rats
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / physiology
  • Second Messenger Systems


  • Eukaryotic Initiation Factor-2B
  • Inositol Phosphates
  • RGS Proteins
  • RGS2 protein, rat
  • Receptors, G-Protein-Coupled
  • Phenylephrine
  • Cyclic AMP
  • Isoproterenol