Glucose de-repression by yeast AMP-activated protein kinase SNF1 is controlled via at least two independent steps
Artikel i vetenskaplig tidskrift, 2014

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.

UPSTREAM KINASES

glucose repression

PHOSPHATASE TYPE-1

quantitative analysis protein kinase

LOOP PHOSPHORYLATION

AMPK

ENERGY SENSOR

SACCHAROMYCES-CEREVISIAE

SNF1

GENE-EXPRESSION

metabolic regulation

MIG1 REPRESSOR

REGULATES PHOSPHORYLATION

FUNCTIONAL DOMAINS

SUC2 GENE

Författare

Raúl Garcia-Salcedo

Göteborgs universitet

T. Lubitz

Gemma Beltran

Göteborgs universitet

Karin Elbing

Göteborgs universitet

Ye Tian

Göteborgs universitet

S. Frey

O. Wolkenhauer

Marcus Krantz

Edda Klipp

Stefan Hohmann

Göteborgs universitet

FEBS Journal

1742-464X (ISSN) 1432-1033 (eISSN)

Vol. 281 7 1901-1917

Ämneskategorier

Biokemi och molekylärbiologi

DOI

10.1111/febs.12753

Mer information

Skapat

2017-10-10