Adenylate cyclase stimulating agents and mitogens raise fructose 2,6-bisphosphate levels in human fibroblasts. Evidence for a dual control of the metabolite.
Fructose 2,6-bisphosphate, the most potent activator of 6-phosphofructo-1-kinase, has been demonstrated to mediate the increase of glycolytic flux induced by mitogens human fibroblasts. In the present work the molecular basis of transmembrane control of fructose 2,6-bisphosphate has been investigated. Prostacyclin and isoprenaline, known to activate adenylate cyclase, are able to increase fructose 2,6-bisphosphate levels, indicating that in human fibroblasts cyclic AMP plays a positive role in the control of the metabolite concentration, opposite to that exerted in hepatocytes. Substances known to activate protein kinase C such as phorbol 12-myristate 13-acetate, or to stimulate phosphoinositide turnover such as thrombin and bradykinin are also effective in raising fructose 2,6-bisphosphate. Therefore, we conclude that cyclic AMP and protein kinase C are likely involved in the control of fructose 2,6-bisphosphate levels in human fibroblasts.
Bruni
P
P
Institute of Biochemistry, University of Florence, Italy.
Vasta
V
V
Farnararo
M
M
D000262:Adenylyl Cyclases / Q000378:metabolism*; D001920:Bradykinin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005635:Fructosediphosphates / Q000378:metabolism*; D006598:Hexosediphosphates / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013917:Thrombin / Q000502:physiology*
D005635:Fructosediphosphates; D006598:Hexosediphosphates; C027652:fructose 2,6-diphosphate; D000242:Cyclic AMP; D013917:Thrombin; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate; D001920:Bradykinin