STIM2 interacts with AMPK and regulates calcium‐induced AMPK activation

What is it about?

AMP-activated protein kinase (AMPK) is a protein complex that can sense the lack of energy in our cells. Low energy levels in our cells can activate AMPK, which then initiate a series of downstream signaling events to restore energy homeostasis so that cells can adapt to low-energy conditions. Dysregulation of this pathway is associated with various human diseases including cancer and diabetes. Calcium, another important signaling molecule in our cells, can also activate AMPK, although how calcium activates AMPK remains unclear. In this study we show that AMPK can physically interact with a calcium sensor protein called STIM2, and propose that STIM2 might act as a bridge to connect AMPK to another protein called calcium/calmodulin-dependent protein kinase 2 (CAMKK2), which can directly activate AMPK in response to calcium stimulation. We find that, when STIM2 is depleted in cells, CAMKK2 and AMPK can no longer "stay together" and calcium cannot activate AMPK appropriately. Our study thus explains how calcium activates AMPK and might have implications to AMPK-associated diseases such as cancer and diabetes.

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