title: The mammalian AMP-activated protein kinase complex mediates glucose regulation of gene expression in the yeast Saccharomyces cerevisiae.
abstract: The AMP-activated protein kinase (AMPK) controls energy homeostasis in eukaryotic cells. Here we expressed hetero-trimeric mammalian AMPK complexes in a Saccharomyces cerevisiae mutant lacking all five genes encoding yeast AMPK/SNF1 components. Certain mammalian complexes complemented the growth defect of the yeast mutant on non-fermentable carbon sources. Phosphorylation of the AMPK α1-subunit was glucose-regulated, albeit not by the Glc7-Reg1/2 phosphatase, which performs this function on yeast AMPK/SNF1. AMPK could take over SNF1 function in glucose derepression. While indirectly acting anti-diabetic drugs had no effect on AMPK in yeast, compound 991 stimulated α1-subunit phosphorylation. Our results demonstrate a remarkable functional conservation of AMPK and that glucose regulation of AMPK may not be mediated by regulatory features of a specific phosphatase.
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, S-40530 Göteborg, Sweden.
authors.forename: Tian
authors.initials: T
authors.lastname: Ye
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, S-40530 Göteborg, Sweden.
authors.forename: Loubna
authors.initials: L
authors.lastname: Bendrioua
authors.affiliation: MRC Clinical Sciences Centre, Cellular Stress Group, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: David
authors.initials: D
authors.lastname: Carmena
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, S-40530 Göteborg, Sweden.
authors.forename: Raúl
authors.initials: R
authors.lastname: García-Salcedo
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, S-40530 Göteborg, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Dahl
authors.affiliation: MRC Clinical Sciences Centre, Cellular Stress Group, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: David
authors.initials: D
authors.lastname: Carling
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Box 462, S-40530 Göteborg, Sweden. Electronic address: stefan.hohmann@gu.se.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hohmann
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D054645:Protein Phosphatase 1 / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C092048:GLC7 protein, S cerevisiae; D054645:Protein Phosphatase 1; C070829:REG1 protein, S cerevisiae; D005947:Glucose
keywords: AMP-activated protein kinase; Active compounds; Invertase activity; Mig1 transcriptional repressor; Saccharomyces cerevisiae; Salt stress; Snf1 protein kinase