AMPK--sensing energy while talking to other signaling pathways.

AMPK--sensing energy while talking to other signaling pathways.
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DOI:
10.1016/j.cmet.2014.09.013
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发表时间:
2014-12-02
期刊:
影响因子:
29
通讯作者:
Hardie DG
Hardie DG
中科院分区:
生物学1区
文献类型:
--
作者:
Hardie DG

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AMP激活的蛋白激酶是细胞能量和营养状态的感受器,在真核生物中几乎普遍表达为由催化(α)和调节(β和γ)亚基组成的异源三聚体复合体。AMPK可能是真核生物进化过程中出现的最早的信号通路之一,与雷帕霉素靶标复合体-1(MTORC1)一样,AMPK可能是最早的信号通路之一。最近的晶体结构为AMPK受磷酸化和变构激活剂调控的机制提供了洞察力。另一个最新的发展是认识到AMPK的激活可能主要不是发生在细胞质中,而是发生在溶酶体的表面,其中AMPK和mTORC1以一种相互调节的方式受到营养物质的可获得性的调节。同样清楚的是,AMPK通路和其他促进细胞生长和增殖的信号通路之间存在大量的串扰,这一点将被讨论。
The AMP-activated protein kinase (AMPK) is a sensor of cellular energy and nutrient status, expressed almost universally in eukaryotes as heterotrimeric complexes comprising catalytic (α) and regulatory (β and γ) subunits. Along with the mechanistic target-of-rapamycin complex-1 (mTORC1), AMPK may have been one of the earliest signaling pathways to have arisen during eukaryotic evolution. Recent crystal structures have provided insights into the mechanisms by which AMPK is regulated by phosphorylation and allosteric activators. Another recent development has been the realization that activation of AMPK by the upstream kinase LKB1 may primarily occur not in the cytoplasm but at the surface of the lysosome, where AMPK and mTORC1 are regulated in a reciprocal manner by the availability of nutrients. It is also becoming clear that there is a substantial amount of crosstalk between the AMPK pathway and other signaling pathways that promote cell growth and proliferation, and this will be discussed.
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