Dual role of phosphofructokinase-2/fructose bisphosphatase-2 in regulating the compartmentation and expression of glucokinase in hepatocytes.

نویسندگان

  • Victoria A Payne
  • Catherine Arden
  • Chaodong Wu
  • Alex J Lange
  • Loranne Agius
چکیده

Hepatic glucokinase is regulated by a 68-kDa regulatory protein (GKRP) that is both an inhibitor and nuclear receptor for glucokinase. We tested the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2) in regulating glucokinase compartmentation in hepatocytes. PFK2 catalyzes formation or degradation of the regulator of glycolysis fructose 2,6-bisphosphate (fructose 2,6-P2), depending on its phosphorylation state (ser-32), and is also a glucokinase-binding protein. Incubation of hepatocytes at 25 mmol/l glucose causes translocation of glucokinase from the nucleus to the cytoplasm and an increase in fructose 2,6-P2. Glucagon caused phosphorylation of PFK2-ser-32, lowered the fructose 2,6-P2 concentration, and inhibited glucose-induced translocation of glucokinase. These effects of glucagon were reversed by expression of a kinase-active PFK2 mutant (S32A/H258A) that overrides the suppression of fructose 2,6-P2 but not by overexpression of wild-type PFK2. Overexpression of PFK2 potentiated glucokinase expression in hepatocytes transduced with an adenoviral vector-encoding glucokinase by a mechanism that does not involve stabilization of glucokinase protein from degradation. It is concluded that PFK2 has a dual role in regulating glucokinase in hepatocytes: it potentiates glucokinase protein expression by posttranscriptional mechanisms and favors its cytoplasmic compartmentation. Thus, it acts in a complementary mechanism to GKRP, which also regulates glucokinase protein expression and compartmentation.

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Contributions of glucokinase and phosphofructokinase-2/fructose bisphosphatase-2 to the elevated glycolysis in hepatocytes from Zucker fa/fa rats.

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The contributions of glucokinase and phosphofructokinase-2/fructose bisphosphatase-2 to the elevated glycolysis in hepatocytes from Zucker fa/fa rats

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عنوان ژورنال:
  • Diabetes

دوره 54 7  شماره 

صفحات  -

تاریخ انتشار 2005