analysis of glucokinase/6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase complex formation, binding and activation of GK by PFK-2/FBPase-2 in beta-cells is promoted by glucose, resulting in an enhancement of insulin secretion at stimulatory glucose concentrations, without affecting basal insulin secretion
flux through phosphofructokinase-1 is controlled by the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 via production/degradation of fructose-2,6-bisphosphate, a potent allosteric activator of phosphofructokinase-1, as well as direct activation of glucokinase due to a protein-protein interaction
PFKFB2 has a critical role in glucose uptake and glucose-dependent lipid synthesis. Induction of de novo lipid synthesis by androgen requires the transcriptional up-regulation of HK2 and PFKFB2, and phosphorylation of PFKFB2 generated by the PI3K/Akt signalling pathway to supply the source for lipogenesis from glucose in prostate cancer cells
fructose-2,6-bisphosphate synthesis by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 is required for the glycolytic response to hypoxia and tumor growth
PFK2/FBPase2 is most helpful to the glucose-sensing capacity of glucokinase in a fasted organism, or in the transition to threshold as glucose is elevated during feeding
both a PFKFB3 inhibitor or PFKFB3 silencing by siRNA suppress the basal and the H2O2-induced autophagy concomitantly with the inhibition of AMPK activity. Overexpression of wild-type PFKFB3 promotes H2O2-induced autophagy, but mutant K472/473A, which lost nuclear localizing property, inhibits the autophagic process. The K472/473A mutant stimulates more lactate production, and decreases the activity of AMPK compared to the wild-type
overexpression of microRNA miR-26b represses PFKFB3 mRNA and protein levels followed by modulation of the expression of glycolytic components such as LDHA, GLUT-1 and markers of invasion and cell cycle such as MMP-9, MMP-2, cyclin D1 and p27. The binding site for miR-26b is predicted in the 3'-untranslated region of the PFKFB3 gene
TIGAR potently inhibits NF-kappaB-dependent gene expression by suppressing the upstream activation of IKKbeta phosphorylation and kinase activation. Inhibition occurs through a direct binding competition between NEMO and TIGAR for association with the linear ubiquitination assembly complex LUBAC. A TIGAR phosphatase activity-deficient mutant is equally effective as wild-type TIGAR in inhibiting NEMO linear ubiquitination. TIGAR knockout mice display enhanced adipose tissue NF-kappaB signaling, and adipocyte-specific overexpression of TIGAR suppresses adipose tissue NF-kappaB signaling
Transforming growth factor TGFbeta1 induces isoform PFKFB3 expression and stimulates glycolysis in Panc1 cells. siRNA silencing of PFKFB3 prevents the stimulation of glycolysis and in vitro invasion ability of Panc1 cells by TGFbeta1. PFKFB3 silencing suppresses the TGFbeta1-mediated induction of the Snail protein
tumor suppressor p53 regulates the expression of PFKFB4 and p53-deficient cancer cells are highly dependent on the function of the enzyme. Depletion of PFKFB4 from p53-deficient cancer cells increases levels of fructose-2,6-bisphosphate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose-phosphate pathway. PFKFB4 is also required to support the synthesis and regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) in p53-deficient cancer cells. Depletion of PFKFB4-attenuates cellular biosynthetic activity and results in the accumulation of reactive oxygen species and cell death in the absence of p53. Silencing of PFKFB4-induces apoptosis in p53-deficient cancer cells in vivo and interferes with tumor growth
androgen stimulates glycolysis for de novo lipid synthesis by increasing the activities of hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2, up-regulation of PFKFB2 expression is mediated by the direct binding of ligand-activated androgen receptor to the PFKFB2 promoter