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STIM2 interacts with AMPK and regulates calcium‐induced AMPK activation
Author(s) -
Chauhan Anoop Singh,
Liu Xiaoguang,
Jing Ji,
Lee Hyemin,
Yadav Raj Kumar,
Liu Jindou,
Zhou Yubin,
Gan Boyi
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201801225r
Subject(s) - ampk , protein kinase a , microbiology and biotechnology , chemistry , amp activated protein kinase , calcium , regulator , kinase , biochemistry , biology , organic chemistry , gene
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. FASEB J. 33, 2957–2970 (2019). www.fasebj.org