title: Glucose de-repression by yeast AMP-activated protein kinase SNF1 is controlled via at least two independent steps.
abstract: The AMP-activated protein kinase, AMPK, controls energy homeostasis in eukaryotic cells but little is known about the mechanisms governing the dynamics of its activation/deactivation. The yeast AMPK, SNF1, is activated in response to glucose depletion and mediates glucose de-repression by inactivating the transcriptional repressor Mig1. Here we show that overexpression of the Snf1-activating kinase Sak1 results, in the presence of glucose, in constitutive Snf1 activation without alleviating glucose repression. Co-overexpression of the regulatory subunit Reg1 of the Glc-Reg1 phosphatase complex partly restores glucose regulation of Snf1. We generated a set of 24 kinetic mathematical models based on dynamic data of Snf1 pathway activation and deactivation. The models that reproduced our experimental observations best featured (a) glucose regulation of both Snf1 phosphorylation and dephosphorylation, (b) determination of the Mig1 phosphorylation status in the absence of glucose by Snf1 activity only and (c) a regulatory step directing active Snf1 to Mig1 under glucose limitation. Hence it appears that glucose de-repression via Snf1-Mig1 is regulated by glucose via at least two independent steps: the control of activation of the Snf1 kinase and directing active Snf1 to inactivating its target Mig1.
authors: Department of Chemistry and Molecular Biology, University of Gothenburg, Sweden.
authors: Raúl
authors: R
authors: García-Salcedo
authors: Timo
authors: T
authors: Lubitz
authors: Gemma
authors: G
authors: Beltran
authors: Karin
authors: K
authors: Elbing
authors: Ye
authors: Y
authors: Tian
authors: Simone
authors: S
authors: Frey
authors: Olaf
authors: O
authors: Wolkenhauer
authors: Marcus
authors: M
authors: Krantz
authors: Edda
authors: E
authors: Klipp
authors: Stefan
authors: S
authors: Hohmann
mesh_terms: D005947:Glucose / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C085976:MIG1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C071570:SNF1-related protein kinases; C094326:PRK1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D054645:Protein Phosphatase 1; C070829:REG1 protein, S cerevisiae; D005947:Glucose
keywords: AMPK/SNF1; glucose repression; metabolic regulation; quantitative analysis protein kinase