title: PF-4708671 activates AMPK independently of p70S6K1 inhibition.
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.
authors.affiliation: Department of Pathology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: Gilad W
authors.initials: GW
authors.lastname: Vainer
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, and Department of Genetics and Metabolic Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Ann
authors.initials: A
authors.lastname: Saada
authors.affiliation: Department of Pathology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
authors.forename: Juliane
authors.initials: J
authors.lastname: Kania-Almog
authors.affiliation: Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Adir
authors.initials: A
authors.lastname: Amartely
authors.affiliation: Human Nutrition and Metabolism, Hebrew University Medical School, Jerusalem, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Bar-Tana
authors.affiliation: Human Nutrition and Metabolism, Hebrew University Medical School, Jerusalem, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Hertz
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D007093:Imidazoles; D046912:Multiprotein Complexes; C552719:PF-4708671; D010879:Piperazines; D000076222:Mechanistic Target of Rapamycin Complex 1; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases