Fernandez-Garcia P, Pelaez R, Herrero P, Moreno F

Nucleocytoplasmic shuttling of Hxk2 induced by glucose levels has been reported recently. Here we present evidence which indicates that Hxk2 nucleocytoplasmic traffic is regulated by phosphorylation and dephosphorylation at serine-14. Moreover, we have identified the protein kinase Snf1 and the protein phosphatase Glc7-Reg1 as novel regulatory partners for the nucleocytoplasmic ...

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shuttling of Hxk2. Functional studies reveal that, in contrast to the wild-type protein, the dephosphorylation-mimicking mutant of Hxk2 retains its nuclear localization in low-glucose conditions and the phosphomimetic mutant of Hxk2 retains its cytoplasmic localization in high-glucose conditions. Interaction experiments of Hxk2 with Kap60 and Xpo1 indicate that nuclear import of the S14D mutant of Hxk2 is severely decreased but the export is significantly enhanced. Conversely, nuclear import of the S14A mutant of Hxk2 is significantly enhanced, although the export is severely decreased. The interaction of Hxk2 with Kap60 and Xpo1 was found to occur in the dephosphorylated and phosphorylated states of the protein, respectively. In addition, we found that Hxk2 is a substrate for Snf1. Mutational analysis indicates that serine-14 is a major in vitro and in vivo phosphorylation site for Snf1. We also provide evidence that dephosphorylation of Hxk2 at serine-14 is a protein phosphatase Glc7-Reg1 dependent process. Taken together, this study establishes a functional link between Hxk2, Reg1 and Snf1 signaling, which involves the regulation of Hxk2 nucleocytoplasmic shuttling by phosphorylation-dephosphorylation of serine-14.

Date: Oct. 12, 2012

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