PF-4708671 Activates AMPK Independently of p70S6K1 Inhibition |
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| Authors: | Gilad W Vainer Ann Saada Juliane Kania-Almog Adir Amartely Jacob Bar-Tana Rachel Hertz |
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| Institution: | 1. Department of Pathology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.; 2. Monique and Jacques Roboh Department of Genetic Research, and Department of Genetics and Metabolic Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.; 3. Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.; 4. Human Nutrition and Metabolism, Hebrew University Medical School, Jerusalem, Israel.; Mayo Clinic, United States of America, |
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| Abstract: | The P70 ribosomal protein S6 kinase 1 (P70S6K1) is activated by the mammalian target of rapamycin (mTORC1) and regulates proliferation, growth, and metabolism. PF-4708671 is a novel, cell-permeable, has been proposed to be a highly specific inhibitor of p70S6K1. It is used in micromolar concentration range to dissect signaling pathways downstream of mTORC1 and to study the function of p70S6K1. Here we show that PF-4708671 induces AMP-activated protein kinase (AMPK) phosphorylation and activation in immortalized mouse embryonic fibroblasts (MEF) independently of p70S6K1, due to specific inhibition of mitochondrial respiratory chain Complex I. |
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