Hxk2 regulates the phosphorylation state of Mig1 and therefore its nucleocytoplasmic distribution.
Mig1 and Hxk2 are two major mediators of glucose repression in Saccharomyces cerevisiae. However, the mechanism by which Hxk2 participates in the glucose repression signaling pathway is not completely understood. Recently, it has been demonstrated that Hxk2 interacts with Mig1 to generate a repressor complex located in the nucleus of S. cerevisiae. However, the mechanism by which Mig1 favors the presence of Hxk2 in the nucleus is not clear, and the function of Hxk2 at the nuclear repressor complex level is still unknown. Here, we report that serine 311 of Mig1 is a critical residue for interaction with Hxk2 and that this interaction is regulated by glucose. Our findings suggest that Snf1 interacts constitutively with the Hxk2 component of the repressor complex at high and low glucose conditions. Furthermore, we show that Snf1 binds to Mig1 under low glucose conditions and that binding is largely abolished after a shift to high glucose medium. We found that phosphorylation of serine 311 of Mig1 by Snf1 kinase is essential for Mig1 protein nuclear export and derepression of the SUC2 gene in glucose-limited cells. These results allow postulating that the Hxk2 operates by interacting both with Mig1 and Snf1 to inhibit the Mig1 phosphorylation at serine 311 during high glucose grown.
Ahuatzi
Deifilia
D
Departamento de Bioqui´mica y Biologi´a Molecular, Universidad de Oviedo, Campus del Cristo, Edificio Santiago Gasco´n, 33006 Oviedo, Spain.
Riera
Alberto
A
Departamento de Bioqui´mica y Biologi´a Molecular, Universidad de Oviedo, Campus del Cristo, Edificio Santiago Gasco´n, 33006 Oviedo, Spain.
Pela Ez
Rafael
R
Departamento de Bioqui´mica y Biologi´a Molecular, Universidad de Oviedo, Campus del Cristo, Edificio Santiago Gasco´n, 33006 Oviedo, Spain.
Herrero
Pilar
P
Departamento de Bioqui´mica y Biologi´a Molecular, Universidad de Oviedo, Campus del Cristo, Edificio Santiago Gasco´n, 33006 Oviedo, Spain.
Moreno
Fernando
F
Departamento de Bioqui´mica y Biologi´a Molecular, Universidad de Oviedo, Campus del Cristo, Edificio Santiago Gasco´n, 33006 Oviedo, Spain. Electronic address: fmoreno@uniovi.es.
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006593:Hexokinase / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D043324:beta-Fructofuranosidase / Q000378:metabolism
D004268:DNA-Binding Proteins; C085976:MIG1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C071570:SNF1-related protein kinases; C490214:HXK2 protein, S cerevisiae; D006593:Hexokinase; D017346:Protein Serine-Threonine Kinases; C468437:SUC2 protein, S cerevisiae; D043324:beta-Fructofuranosidase; D005947:Glucose