Lipovka, YuliaChen, HaoVagner, JosefPrice, Theodore J. (UT Dallas)Tsao, Tsu-ShuenKonhilas, John P.2017-02-282017-02-282015-09-151573-4935http://hdl.handle.net/10735.1/5316Includes supplementary materialNormal and pathological stressors engage the AMP-activated protein kinase (AMPK) signaling axis to protect the cell from energetic pressures. Sex steroid hormones also play a critical role in energy metabolism and significantly modify pathological progression of cardiac disease, diabetes/obesity, and cancer. AMPK is targeted by17β-estradiol (E2), the main circulating estrogen, but the mechanism by which E2 activates AMPK is currently unknown. Using an estrogen receptor α/β (ERα/β) positive (T47D) breast cancer cell line, we validated E2-dependent activation of AMPK that was mediated through ERα (not ERβ) by using three experimental strategies. A series of co-immunoprecipitation experiments showed that both ERs associated with AMPK in cancer and striated (skeletal and cardiac) muscle cells. We further demonstrated direct binding of ERs to the α-catalytic subunit of AMPK within the βγ-subunit binding domain. Finally, both ERs interacted with the upstream LKB1 kinase complex, which is required for E2-dependent activation of AMPK. We conclude that estradiol activates AMPK through ERα by direct interaction with the βγ-binding domain of AMPKα.; Copyright 2015 The Author(s).CC BY 3.0 (Attribution)©2015 The Authorshttp://creativecommons.org/licenses/by/3.0/AMP-Activated Protein KinasesReceptors, EstrogenBreast NeoplasmsEstradiolPhosphorylationTextLipovka, Yulia, Hao Chen, Josef Vagner, Theodore J. Price, et al. 2015. "Oestrogen receptors interact with the α-catalytic subunit of AMP-activated protein kinase." Bioscience Reports (2015), doi:10.1042/BSR20150074