Mechanisms for increased levels of phosphorylation of elongation factor-2 during hibernation in ground squirrels.
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.
Chen
Y
Y
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4128, USA.
Matsushita
M
M
Nairn
A C
AC
Damuni
Z
Z
Cai
D
D
Frerichs
K U
KU
Hallenbeck
J M
JM
D000818:Animals; D001921:Brain / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002384:Catalysis; D003600:Cytosol / Q000201:enzymology; D054736:Elongation Factor 2 Kinase; D006605:Hibernation / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D020652:Peptide Elongation Factor 2 / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D021122:Protein Subunits; D012589:Sciuridae / Q000502:physiology*
D020652:Peptide Elongation Factor 2; D021122:Protein Subunits; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D054736:Elongation Factor 2 Kinase; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2