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

Mechanisms for increased levels of phosphorylation of elongation factor-2 during hibernation in ground squirrels
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DOI:
10.1021/bi010649w
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发表时间:
2001-09-25
期刊:
影响因子:
2.9
通讯作者:
Hallenbeck, JM
Hallenbeck, JM
中科院分区:
生物学3区
文献类型:
--
作者:
Chen, Y;Matsushita, M;Hallenbeck, JM

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以前,eEF-2磷酸化已被确定为参与抑制翻译延伸期的可逆机制。在这项研究中,在冬眠的地松鼠的大脑和肝脏中观察到真核细胞延伸因子-2(eEF-2)的磷酸化水平增加。在冬眠动物的大脑和肝脏中,eEF-2激酶活性相对于活跃动物增加。蛋白磷酸酶2A(PP 2A),一种使eEF-2去磷酸化的磷酸酶,在冬眠动物的大脑和肝脏中的活性也降低了。这与PP 2A的抑制剂2(I-2(PP 2A))水平的增加有关,尽管在冬眠的大脑和肝脏中PP 2A的催化亚基(PP 2A/C)水平增加。这些结果表明,eEF-2磷酸化代表了一个特定的和以前未知的机制,在冬眠过程中的蛋白质合成的延伸阶段的抑制。冬眠动物中eEF-2磷酸化水平的增加似乎是细胞功能调节性关闭的一个组成部分,其允许冬眠动物耐受脑血流量和氧输送能力的严重降低。
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.