Oestrogen Receptors Interact with the α-Catalytic Subunit of AMP-Activated Protein Kinase

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Portland Press on behalf of the Biochemical Society

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).

Includes supplementary material
AMP-Activated Protein Kinases, Receptors, Estrogen, Breast Neoplasms, Estradiol, Phosphorylation
NIH grant [no. HL098256]; National Mentored Research Science Development Award [K01 AR052840] and Independent Scientist Award [no. K02 HL105799]; NIH/NCRR grant [no. 1S10 RR028868-01].
CC BY 3.0 (Attribution), ©2015 The Authors