TY - JOUR
T1 - PF-4708671 activates AMPK independently of p70S6K1 inhibition
AU - Vainer, Gilad W.
AU - Saada, Ann
AU - Kania-Almog, Juliane
AU - Amartely, Adir
AU - Bar-Tana, Jacob
AU - Hertz, Rachel
N1 - Publisher Copyright:
© 2014 Vainer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2014/9
Y1 - 2014/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84929941964&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0107364
DO - 10.1371/journal.pone.0107364
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C2 - 25202971
AN - SCOPUS:84929941964
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 9
M1 - e107364
ER -
