Jl. Rosa et al., REGULATION OF HEPATIC 6-PHOSPHOFRUCTO-2-KINASE FRUCTOSE 2,6-BISPHOSPHATASE GENE-EXPRESSION BY GLUCAGON, The Journal of biological chemistry, 268(30), 1993, pp. 22540-22545
The control of hepatic 6-phosphofructo-2-kinase/fructose 2,6-bisphosph
atase gene expression by glucagon was studied. Intraperitoneal adminis
tration of glucagon rapidly decreased the fructose 2,6-bisphosphate co
ntent by phosphorylation of 6-phosphofructo-2-kinase/fructose 2,6-bisp
hosphatase and diminution of its V(max). Immunologic studies using a s
pecific liver antibody showed that the amount of enzyme rapidly decrea
sed. Northern blot analysis showed that the isozyme expressed is the a
dult liver form. The 6-phosphofructo-2-kinase/fructose 2,6-bisphosphat
ase mRNA content decreased, whereas that of phosphoenolpyruvate carbox
ykinase increased, and that of albumin did not change. Run-on transcri
ption assays with isolated nuclei showed inhibition in the relative tr
anscription rate of the 6-phosphofructo-2-kinase/fructose 2,6-bisphosp
hatase gene and a stimulation of phosphoenolpyruvate carboxykinase gen
e. The regulation of mRNA stability of 6-phosphofructo-2-kinase/fructo
se 2,6-bisphosphatase by glucagon was also studied. The half-life of m
RNA decreased in the presence of glucagon, suggesting that proteins mo
dulated by a glucagon-dependent process are regulating its stability.
The time course of mRNA levels correlated with the transcription inhib
ition of gene and destabilization of mRNA, indicating that glucagon mo
dulates 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase gene expr
ession at both transcriptional and posttranscriptional levels.