Browsing by Author "Price, Theodore J. (UT Dallas)"
Now showing 1 - 1 of 1
- Results Per Page
- Sort Options
Item Oestrogen Receptors Interact with the α-Catalytic Subunit of AMP-Activated Protein Kinase(Portland Press on behalf of the Biochemical Society) Lipovka, Yulia; Chen, Hao; Vagner, Josef; Price, Theodore J. (UT Dallas); Tsao, Tsu-Shuen; Konhilas, John P.Normal 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).