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Volume 272, Number 5, Issue of January 31, 1997 pp. 2846-2851
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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Effect of Growth Factors on the Expression of 6-Phosphofructo2-kinase/Fructose-2,6-bisphosphatase in Rat-1 Fibroblasts

(Received for publication, August 6, 1996, and in revised form, October 4, 1996)

Manel Joaquin , Cristina Salvado , Beatriz Bellosillo , Alex J. Lange , Joan Gil and Albert Tauler

From the Unitat de Bioquímica, Departament de Ciències Fisiològiques Humanes i de la Nutriciò, Universitat de Barcelona, Avinguda Diagonal 643, Barcelona 08028, Catalunya, Spain and the  Department of Biochemistry, University of Minnesota, Minneapolis, Minnesota 55455-0347

The activation of glycolytic flux is a biochemical characteristic of growing cells. Several reports have demonstrated the role of fructose 2,6-bisphosphate in this process. In this paper we show that the levels of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (6PF2K/Fru-2,6-P₂ase) mRNA are modulated in response to serum and growth factors and this effect is due to regulation of its transcription rate. The modulation of the expression of this enzyme by growth factors differs according their mitogenic effect; both lysophosphatidic acid and epidermal growth factor, when added alone, increased the mRNA levels, but endothelin had no effect. Furthermore, cAMP, which acts as an antimitogenic signal in Rat-1 fibroblasts, produced a decrease in 6PF2K/Fru-2,6-P₂ase mRNA and inhibited the effects of lysophosphatidic acid and epidermal growth factor on 6PF2K/Fru-2,6-P₂ase expression. PD 098059, a specific inhibitor of the activation of the mitogen-activated protein kinase, was able to prevent the effect of EGF on 6PF2K/Fru-2,6-P₂ase gene expression. These results imply that activation of mitogen-activated protein kinase is required for the stimulation of the transcription of 6PF2K/Fru-2,6-P₂ase by EGF.

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