Oestrogen receptors interact with the α-catalytic subunit of AMP-activated protein kinase

Yulia Lipovka, Hao Chen, Josef Vagner, Theodore J. Price, Tsu Shuen Tsao, John P. Konhilas

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Normal and pathological stressors engage the AMP-activated protein kinase (AMPK) signalling 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 by 17β-oestradiol (E2), the main circulating oestrogen, but the mechanism by which E2 activates AMPK is currently unknown. Using an oestrogen 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 liver kinase B 1 (LKB1) kinase complex, which is required for E2-dependent activation of AMPK. We conclude that E2 activates AMPK through ERα by direct interaction with the βγ-binding domain of AMPKα.

Original languageEnglish (US)
JournalBioscience reports
Volume35
Issue number5
DOIs
StatePublished - Sep 15 2015
Externally publishedYes

Fingerprint

AMP-Activated Protein Kinases
Estrogen Receptors
Catalytic Domain
Phosphotransferases
Chemical activation
Cells
Gonadal Steroid Hormones
Medical problems
Immunoprecipitation
Cardiac Myocytes
Liver
Energy Metabolism
Muscle
Estradiol
Heart Diseases
Neoplasms
Estrogens
Skeletal Muscle
Obesity
Breast Neoplasms

Keywords

  • AMP-activated protein kinase (AMPK)
  • breast cancer
  • oestradiol
  • oestrogen receptors

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Oestrogen receptors interact with the α-catalytic subunit of AMP-activated protein kinase. / Lipovka, Yulia; Chen, Hao; Vagner, Josef; Price, Theodore J.; Tsao, Tsu Shuen; Konhilas, John P.

In: Bioscience reports, Vol. 35, No. 5, 15.09.2015.

Research output: Contribution to journalArticle

Lipovka, Yulia ; Chen, Hao ; Vagner, Josef ; Price, Theodore J. ; Tsao, Tsu Shuen ; Konhilas, John P. / Oestrogen receptors interact with the α-catalytic subunit of AMP-activated protein kinase. In: Bioscience reports. 2015 ; Vol. 35, No. 5.
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