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A431 cells were treated with epidermal growth factor (EGF) to study the mechanism by which this factor accelerates the glycolytic flux. After EGF treatment, fructose-2,6-bisphosphate (Fru-2,6-P2) levels rose up to 2-fold. This change correlated with an increase in phosphofructokinase-2 activity, which was not due to a change in the transcription or translation of the enzyme, neither in the amount of enzyme. PK-C does not appear to be involved in the signalling mechanism since EGF was equally potent in PK-C depleted cells than in control cells. The increase in Fru-2,6-P2 levels was lower and more transient in cells treated with EGF in a calcium-free medium than in the presence of the cation, and it was restored by the addition of calcium to the medium. These results suggest a possible role for calcium-mediated pathways in the control of Fru-2,6-P2 levels in A431 cells.

The use of NIH3T3 fibroblasts overexpressing different mutations of the EGF receptor shows that regulation of fructose-2,6-bisphosphate (Fru-2,6-P2) metabolism by EGF is mediated by the kinase activity of the EGF receptor and suggests a PLCγ1-mediated mechanism. The effect of several extracellular matrix components on glucose metabolism was assessed by incubating A431 cells and NIH3T3 fibroblasts with heparin, laminin, fibronectin, collagen and PG-I and PG-II proteoglycans and measuring the levels of Fru-2,6-P2. Laminin increased the levels of Fru-2,6-P2 and heparin decreased the levels of the metabolite, whereas the other molecules did not have any effect. No effect of laminin or heparin in glucose uptake by the cell was observed. Laminin was able to modulate the effects of EGF on Fru-2,6-P2 concentration, suggesting cross-talk between these agents.