Inhibition of glucokinase translocation by AMP-activated protein kinase is associated with phosphorylation of both GKRP and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase

摘要

Various binding proteins of GK have been identified that could act as cytoplasmic binding proteins. They include a dual-specificity protein phosphatase (27) and the bifunctional enzyme PFK2 (7), which catalyzes the formation and degradation of fructose 2,6-P2 (21) and functions as a cytoplasmic binding protein for GK (32). The liver isoform of PFK2 is regulated by phosphorylation of ser-32 by cAMP-dependent kinase (23), which decreases the kinase/bisphosphatase activity ratio, resulting in depletion of fructose 2,6-P2 (21). Glucagon counteracts both the increase in fructose 2,6-P2 caused by elevated glucose and the translocation of GK from the nucleus. These effects are reversed by the expression of a kinase-active PFK2 variant lacking serine-32 (31), as a result of sequestration of GK in the cytoplasm by the dephosphorylated form of PFK2 (32).