Human GKβ (pancreatic β-cell glucokinase) is the main glucose-phosphorylating enzyme in pancreatic β-cells. It shares several structural, catalytic and regulatory properties with Hxk2 (hexokinase 2) from Saccharomyces cerevisiae. In fact, it has been previously described that expression of GKβ in yeast could replace Hxk2 in the glucose signalling pathway of S. cerevisiae. In the present study we report that GKβ exerts its regulatory role by association with the yeast transcriptional repressor Mig1 (multicopy inhibitor of GAL gene expression 1); the presence of Mig1 allows GKβ to bind to the SUC2 (sucrose fermentation 2) promoter, helping in this way in the maintenance of the repression of the SUC2 gene under high-glucose conditions. Since a similar mechanism has been described for the yeast Hxk2, the findings of the present study suggest that the function of the regulatory domain present in these two proteins has been conserved throughout evolution. In addition, we report that GKβ is enriched in the yeast nucleus of high-glucose growing cells, whereas it shows a mitochondrial localization upon removal of the sugar. However, GKβ does not exit the nucleus in the absence of Mig1, suggesting that Mig1 regulates the nuclear exit of GKβ under low-glucose conditions. We also report that binding of GKβ to Mig1 allows the latter protein to be located at the mitochondrial network under low-glucose conditions.
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Research Article|
September 25 2008
Human pancreatic β-cell glucokinase: subcellular localization and glucose repression signalling function in the yeast cell
Alberto Riera;
Alberto Riera
*Departamento de Bioquímica y Biología Molecular. Universidad de Oviedo, 33006-Oviedo, Spain
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Deifilia Ahuatzi;
Deifilia Ahuatzi
1
*Departamento de Bioquímica y Biología Molecular. Universidad de Oviedo, 33006-Oviedo, Spain
2To whom correspondence should be addressed (email fmoreno@uniovi.es).
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Pilar Herrero;
Pilar Herrero
*Departamento de Bioquímica y Biología Molecular. Universidad de Oviedo, 33006-Oviedo, Spain
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Maria Adelaida Garcia-Gimeno;
Maria Adelaida Garcia-Gimeno
†Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (CSIC), Jaime Roig 11, 46010 Valencia, Spain
‡CIBER de Enfermedades Raras (CIBERER), 46010 Valencia, Spain
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Pascual Sanz;
Pascual Sanz
†Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (CSIC), Jaime Roig 11, 46010 Valencia, Spain
‡CIBER de Enfermedades Raras (CIBERER), 46010 Valencia, Spain
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Fernando Moreno
Fernando Moreno
2
*Departamento de Bioquímica y Biología Molecular. Universidad de Oviedo, 33006-Oviedo, Spain
2To whom correspondence should be addressed (email fmoreno@uniovi.es).
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Publisher: Portland Press Ltd
Received:
April 17 2008
Revision Received:
June 11 2008
Accepted:
June 30 2008
Accepted Manuscript online:
June 30 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 415 (2): 233–239.
Article history
Received:
April 17 2008
Revision Received:
June 11 2008
Accepted:
June 30 2008
Accepted Manuscript online:
June 30 2008
Citation
Alberto Riera, Deifilia Ahuatzi, Pilar Herrero, Maria Adelaida Garcia-Gimeno, Pascual Sanz, Fernando Moreno; Human pancreatic β-cell glucokinase: subcellular localization and glucose repression signalling function in the yeast cell. Biochem J 15 October 2008; 415 (2): 233–239. doi: https://doi.org/10.1042/BJ20080797
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