Dual Role of Phosphofructokinase-2/Fructose Bisphosphatase-2 in Regulating the Compartmentation and Expression of Glucokinase in Hepatocytes

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-phos-phofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2) in regulating glucokinase compartmentation in hepato-cytes. PFK2 catalyzes formation or degradation of the regulator of glycolysis fructose 2,6-bisphosphate (fruc-tose 2,6-P2), depending on its phosphorylation state (ser-32), and is also a glucokinase-binding protein. In-cubation 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 o