AMPK: a cellular energy sensor primarily regulated by AMP.
AMPK: a cellular energy sensor primarily regulated by AMP.
复制标题
DOI：
10.1042/bst20130244
复制
发表时间：
2014-03
影响因子：
3.9
通讯作者：
Hardie DG
中科院分区：
文献类型：
--
作者：
Gowans GJ;Hardie DG
AMPK（AMP活化蛋白激酶）是一种细胞能量传感器，可监测细胞内AMP/ATP的比例，也可能是ADP/ATP。一旦被细胞能量水平下降激活，它通过打开产生ATP的分解代谢途径来恢复能量稳态，同时关闭合成代谢途径和其他消耗ATP的过程。AMPK通过三种机制通过AMP的增加而被开启，所有这些机制都被ATP拮抗：（i）通过上游活化激酶促进Thr 172的磷酸化;（ii）通过磷酸酶抑制Thr 172的去磷酸化;和（iii）磷酸化激酶的变构活化。最近，有人提出前两种机制也是由ADP触发的，这可能是生理信号而不是AMP，第三种机制可能没有生理意义。我们重新评估了这些问题，发现只有机制（ii）被ADP模仿，并且ADP也不如AMP有效，我们仍然认为AMP是主要信号。我们还提供了证据表明，机制（iii），即AMP的变构激活，是完整细胞中的一个定量重要机制。
AMPK (AMP-activated protein kinase) is a cellular energy sensor that monitors the ratio of AMP/ATP, and possibly also ADP/ATP, inside cells. Once activated by falling cellular energy levels, it acts to restore energy homoeostasis by switching on catabolic pathways that generate ATP, while switching off anabolic pathways and other processes consuming ATP. AMPK is switched on by increases in AMP via three mechanisms, all of which are antagonized by ATP: (i) promotion of phosphorylation of Thr172by upstream activating kinases; (ii) inhibition of dephosphorylation of Thr172by phosphatases; and (iii) allosteric activation of the phosphorylated kinase. Recently, it has been proposed that the first two mechanisms are also triggered by ADP, which might be the physiological signal rather than AMP, and that the third mechanism may not be physiologically significant. We have re-evaluated these questions, and found that only mechanism (ii) is mimicked by ADP, and that ADP is also less potent than AMP, which we still believe to be the primary signal. We have also provided evidence that mechanism (iii), i.e. allosteric activation by AMP, is a quantitatively significant mechanism in intact cells.