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Göteborgs universitets publikationer

Glucose de-repression by yeast AMP-activated protein kinase SNF1 is controlled via at least two independent steps

Författare och institution:
Raúl Garcia-Salcedo (Institutionen för kemi och molekylärbiologi); T. Lubitz (-); Gemma Beltran (Institutionen för kemi och molekylärbiologi); Karin Elbing (Institutionen för kemi och molekylärbiologi); Ye Tian (Institutionen för kemi och molekylärbiologi); S. Frey (-); O. Wolkenhauer (-); M. Krantz (-); E. Klipp (-); Stefan Hohmann (Institutionen för kemi och molekylärbiologi)
Publicerad i:
Febs Journal, 281 ( 7 ) s. 1901-1917
ISSN:
1742-464X
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2014
Språk:
engelska
Fulltextlänk:
Sammanfattning (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.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
NATURVETENSKAP ->
Biologiska vetenskaper ->
Biokemi och molekylärbiologi ->
Biokemi
Nyckelord:
AMPK, SNF1, glucose repression, metabolic regulation, quantitative analysis protein kinase, SACCHAROMYCES-CEREVISIAE, MIG1 REPRESSOR, PHOSPHATASE TYPE-1, GENE-EXPRESSION, ENERGY SENSOR, SUC2 GENE, REGULATES PHOSPHORYLATION, LOOP PHOSPHORYLATION, FUNCTIONAL DOMAINS, UPSTREAM KINASES
Projekt:
Eukaryotic unicellular organism biology systems biology of the control of cell growth and proliferation (UNICELLSYS ) (EC/FP7/201142) Mer information
Postens nummer:
197744
Posten skapad:
2014-05-08 16:45
Posten ändrad:
2016-08-22 15:41

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