Abstract
Eukaryotic elongation factor 2 (eEF2) kinase (eEF2K) is a key regulator of protein synthesis in mammalian cells. It phosphorylates and inhibits eEF2, the translation factor necessary for peptide translocation during the elongation phase of protein synthesis. When cellular energy demand outweighs energy supply, AMP-activated protein kinase (AMPK) and eEF2K become activated, leading to eEF2 phosphorylation, which reduces the rate of protein synthesis, a process that consumes a large proportion of cellular energy under optimal conditions. The goal of the present study was to elucidate the mechanisms by which AMPK activation leads to increased eEF2 phosphorylation to decrease protein synthesis. Using genetically modified mouse embryo fibroblasts (MEFs), effects of treatments with commonly used AMPK activators to increase eEF2 phosphorylation were compared with that of the novel compound 991. Bacterially expressed recombinant eEF2K was phosphorylated in vitro by recombinant activated AMPK for phosphorylation site-identification by mass spectrometry followed by site-directed mutagenesis of the identified sites to alanine residues to study effects on the kinetic properties of eEF2K. Wild-type eEF2K and a Ser491/Ser492 mutant were retr...Continue Reading
Citations
Jan 19, 2018·Journal of the Royal Society, Interface·D Grahame Hardie
Jul 11, 2019·Open Biology·Diana Vara-CiruelosD Grahame Hardie
Jul 16, 2019·Journal of Alzheimer's Disease : JAD·Qian YuCheng-Xin Gong
Aug 17, 2019·Scientific Reports·Shintaro YamadaNobuyuki Takei
Aug 29, 2019·American Journal of Physiology. Cell Physiology·Nathan HodsonDaniel R Moore
May 1, 2020·EMBO Reports·Sudhriti Ghosh DastidarRavi S Muddashetty
May 8, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Didem Karakas, Bulent Ozpolat
May 21, 2020·Aging Cell·Chen-Ting KuoTsui-Ting Ching
Nov 30, 2019·The Biochemical Journal·Aphrodite T ChoumessiMark H Rider
Dec 12, 2018·Scientific Reports·L KoufariotisS Moore
Apr 17, 2019·Arthritis Research & Therapy·Qi YangYang Wang
Feb 15, 2020·Cell Communication and Signaling : CCS·Min XiaoJing Li
Nov 5, 2017·Molecular Neurodegeneration·Wojciech BobelaBernard L Schneider
Oct 24, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Weiguo DongRuhui Lin
Jun 23, 2020·Oncology Letters·Shujuan TongJianping Chen
Feb 6, 2020·Cell Metabolism·Chen-Song ZhangSheng-Cai Lin
Dec 8, 2020·Biochemistry. Biokhimii︠a︡·S E DmitrievK A Lashkevich
Mar 5, 2020·Cell Metabolism·Asier GonzálezD Grahame Hardie
Apr 4, 2021·International Journal of Molecular Sciences·Mark F McCarty
Mar 8, 2021·FEMS Microbiology Letters·Tatsuomi Matsuoka
Jun 3, 2021·Cells·Maimoona Shahid BhuttaRonen Borenstein
Jun 25, 2021·Journal of Medicinal Chemistry·Shiou ZhuBo Liu
Aug 3, 2021·Frontiers in Microbiology·Carmen StecherChristoph Steininger
Sep 3, 2021·JCI Insight·Khadija BanuMadhav C Menon