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

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dc.contributor.authorLipovka, Yuliaen_US
dc.contributor.authorChen, Haoen_US
dc.contributor.authorVagner, Josefen_US
dc.contributor.authorPrice, Theodore J. (UT Dallas)en_US
dc.contributor.authorTsao, Tsu-Shuenen_US
dc.contributor.authorKonhilas, John P.en_US
dc.date.accessioned2017-02-28T21:06:55Z
dc.date.available2017-02-28T21:06:55Z
dc.date.created2015-09-15
dc.descriptionIncludes supplementary materialen_US
dc.description.abstractNormal 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).en_US
dc.description.sponsorshipNIH 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].en_US
dc.identifier.bibliographicCitationLipovka, 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/BSR20150074en_US
dc.identifier.issn1573-4935en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/5316
dc.publisherPortland Press on behalf of the Biochemical Societyen_US
dc.relation.urihttp://dx.doi.org/10.1042/BSR20150074en_US
dc.rightsCC BY 3.0 (Attribution)en_US
dc.rights©2015 The Authorsen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en_US
dc.source.journalBioscience Reportsen_US
dc.subjectAMP-Activated Protein Kinasesen_US
dc.subjectReceptors, Estrogenen_US
dc.subjectBreast Neoplasmsen_US
dc.subjectEstradiolen_US
dc.subjectPhosphorylationen_US
dc.titleOestrogen Receptors Interact with the α-Catalytic Subunit of AMP-Activated Protein Kinaseen_US
dc.typeTexten_US
dc.type.genrearticleen_US

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