Mechanisms for increased levels of phosphorylation of elongation factor-2 during hibernation in ground squirrels

Biochemistry. 2001 Sep 25;40(38):11565-70. doi: 10.1021/bi010649w.

Abstract

Previously, eEF-2 phosphorylation has been identified as a reversible mechanism involved in the inhibition of the elongation phase of translation. In this study, an increased level of phosphorylation of eukaryotic elongation factor-2 (eEF-2) was observed in the brains and livers of hibernating ground squirrels. In brain and liver from hibernators, eEF-2 kinase activity was increased relative to that of active animals. The activity of protein phosphatase 2A (PP2A), a phosphatase that dephosphorylates eEF-2, was also decreased in brain and liver from hibernators. This was associated with an increase in the level of inhibitor 2 of PP2A (I(2)(PP2A)), although there was an increase in the level of the catalytic subunit of PP2A (PP2A/C) in hibernating brains and livers. These results indicate that eEF-2 phosphorylation represents a specific and previously uncharacterized mechanism for inhibition of the elongation phase of protein synthesis during hibernation. Increased levels of eEF-2 phosphorylation in hibernators appear to be a component of the regulated shutdown of cellular functions that permits hibernating animals to tolerate severe reductions in cerebral blood flow and oxygen delivery capacity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / metabolism*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Catalysis
  • Cytosol / enzymology
  • Elongation Factor 2 Kinase
  • Hibernation / physiology*
  • Liver / metabolism*
  • Peptide Elongation Factor 2 / metabolism*
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Protein Phosphatase 2
  • Protein Subunits
  • Sciuridae / physiology*

Substances

  • Peptide Elongation Factor 2
  • Protein Subunits
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Elongation Factor 2 Kinase
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2