STIM2 interacts with AMPK and regulates calcium-induced AMPK activation.
STIM2 interacts with AMPK and regulates calcium-induced AMPK activation.
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DOI：
10.1096/fj.201801225r
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Gan B
中科院分区：
文献类型：
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作者：
Chauhan AS;Liu X;Jing J;Lee H;Yadav RK;Liu J;Zhou Y;Gan B
AMPK 是能量稳态的重要调节因子，作用于其上游激酶肝激酶 B1 (LKB1) 和钙/钙调蛋白依赖性蛋白激酶 2 (CaMKK2) 的下游。 LKB1在能量应激后主要磷酸化AMPK，而钙介导的AMPK激活需要CaMKK2，尽管钙介导的AMPK激活的调节机制仍不清楚。使用生化、显微镜和遗传学方法，我们证明基质相互作用分子 (STIM)2（一种钙传感器）可作为 CaMKK2-AMPK 信号传导的新型调节剂。我们发现 STIM2 与 AMPK 和 CaMKK2 相互作用，并且细胞内钙水平的增加促进 AMPK 共定位以及与 STIM2 的相互作用。我们进一步表明，STIM2 缺乏会减弱钙诱导的 AMPK 激活，但不会减弱能量应激诱导的 AMPK 激活，这可能是通过调节 CaMKK2-AMPK 相互作用来实现的。总之，我们的结果确定了一种以前未被认识到的调节钙介导的 AMPK 激活的机制。-Chauhan, A. S.、Liu, X.、Jing, J.、Lee, H.、Yadav, R.K.、Liu, J.、Zhou, Y.、Gan B. STIM2 与 AMPK 相互作用并调节钙诱导的 AMPK 激活。
AMPK is a crucial regulator of energy homeostasis that acts downstream of its upstream kinase liver kinase B1 (LKB1) and calcium/calmodulin-dependent protein kinase 2 (CaMKK2). LKB1 primarily phosphorylates AMPK after energy stress, whereas calcium-mediated activation of AMPK requires CaMKK2, although the regulatory mechanisms of calcium-mediated AMPK activation remain unclear. Using biochemical, microscopic, and genetic approaches, we demonstrate that the stromal interaction molecule (STIM)2, a calcium sensor, acts as a novel regulator of CaMKK2-AMPK signaling. We reveal that STIM2 interacts with AMPK and CaMKK2 and that the increase in intracellular calcium levels promotes AMPK colocalization and interaction with STIM2. We further show that STIM2 deficiency attenuates calcium-induced but not energy stress–induced AMPK activation, possibly by regulating the CaMKK2-AMPK interaction. Together, our results identify a previously unappreciated mechanism that modulates calcium-mediated AMPK activation.—Chauhan, A. S., Liu, X., Jing, J., Lee, H., Yadav, R. K., Liu, J., Zhou, Y., Gan B. STIM2 interacts with AMPK and regulates calcium-induced AMPK activation.