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Glucose de‐repression by yeast AMP ‐activated protein kinase SNF 1 is controlled via at least two independent steps
Author(s) -
GarcíaSalcedo Raúl,
Lubitz Timo,
Beltran Gemma,
Elbing Karin,
Tian Ye,
Frey Simone,
Wolkenhauer Olaf,
Krantz Marcus,
Klipp Edda,
Hohmann Stefan
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12753
Subject(s) - ampk , dephosphorylation , protein kinase a , repressor , snf3 , psychological repression , phosphorylation , biochemistry , phosphatase , kinase , microbiology and biotechnology , amp activated protein kinase , chemistry , yeast , biology , saccharomyces cerevisiae , transcription factor , gene expression , gene
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 , SNF 1, 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.

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