Mechanisms for Increased Levels of Phosphorylation of Elongation Factor-2 during Hibernation in Ground Squirrels

• Published in: Biochemistry (Easton) Vol. 40; no. 38; pp. 11565 - 11570
• Main Authors: Chen, Yun, Matsushita, Masayuki, Nairn, Angus C, Damuni, Zahi, Cai, Decheng, Frerichs, Kai U, Hallenbeck, John M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 25.09.2001
• Subjects: Animals; Brain - metabolism; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Catalysis; Cytosol - enzymology; Elongation Factor 2 Kinase; elongation factor EF-2; Hibernation - physiology; Liver - metabolism; Peptide Elongation Factor 2 - metabolism; phosphoprotein phosphatase 2A; Phosphoprotein Phosphatases - metabolism; Phosphorylation; Protein Phosphatase 2; Protein Subunits; Sciuridae - physiology
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi010649w

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 (I2 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.