Joaquin M, Salvado C, Bellosillo B, Lange A J, Gil J, Tauler A
Unitat de Bioquímica, Departament de Ciències Fisiològiques Humanes i de la Nutriciò, Universitat de Barcelona, Avinguda Diagonal 643, Barcelona 08028, Catalunya, Spain.
J Biol Chem. 1997 Jan 31;272(5):2846-51. doi: 10.1074/jbc.272.5.2846.
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.
糖酵解通量的激活是生长中细胞的一种生化特征。多项报告已证实果糖2,6-二磷酸在此过程中的作用。在本文中，我们表明6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶（6PF2K/Fru-2,6-P2ase）mRNA的水平会响应血清和生长因子而受到调节，且这种效应是由于其转录速率的调控所致。生长因子对该酶表达的调节因其促有丝分裂效应而异；单独添加溶血磷脂酸和表皮生长因子时，二者都会增加mRNA水平，但内皮素则无此作用。此外，在大鼠-1成纤维细胞中作为抗有丝分裂信号起作用的cAMP，会使6PF2K/Fru-2,6-P2ase mRNA水平降低，并抑制溶血磷脂酸和表皮生长因子对6PF2K/Fru-2,6-P2ase表达的影响。PD 098059是一种有丝分裂原活化蛋白激酶激活的特异性抑制剂，它能够阻止表皮生长因子对6PF2K/Fru-2,6-P2ase基因表达的作用。这些结果表明，有丝分裂原活化蛋白激酶的激活是表皮生长因子刺激6PF2K/Fru-2,6-P2ase转录所必需的。
