Human pancreatic β-cell glucokinase: subcellular localization and glucose repression signalling function in the yeast cell

Alberto Riera , Deifilia Ahuatzi , Pilar Herrero , Maria Adelaida Garcia-Gimeno , Pascual Sanz , Fernando Moreno (1)

1 Bioquímica y Biología Molecular

Human pancreatic β-cell glucokinase (GKβ) is the main glucose phosphorylating enzyme in pancreatic β-cells. It shares several structural, catalytic and regulatory properties with hexokinase 2 (Hxk2) 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 this study we report that GKβ exerts its regulatory role by association with the yeast transcriptional repressor Mig1; the presence of Mig1 allows GKβ to bind to the SUC2 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, our findings 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.

Mots clés: Life Sciences

Alberto Riera, Deifilia Ahuatzi, Pilar Herrero, Maria Adelaida Garcia-Gimeno, Pascual Sanz, et al.. Human pancreatic β-cell glucokinase: subcellular localization and glucose repression signalling function in the yeast cell. Biochemical Journal, 2008, 415 (2), pp.233-239. ⟨10.1042/BJ20080797⟩. ⟨hal-00479014⟩