CONTROL OF FRUCTOSE 2,6-BISPHOSPHATE METABOLISM BY DIFFERENT MITOGENIC SIGNALS IN SWISS 3T3 FIBROBLASTS

The mitogenic signals that control fructose 2,6-bisphosphate metabolis m in murine Swiss 3T3 fibroblasts have been studied. Bombesin, vasopre ssin, insulin, protein kinase C activation by phorbol esters, or incre ase in the intracellular cAMP concentration by forskolin induced an in crease in fructose 2,6-bisphosphate levels. When the cells were incuba ted in the presence of insulin or phorbol esters, an increase in the V -max of 6-phosphofructo-2-kinase activity was observed. However, forsk olin did not produce this effect. The increase in 6-phosphofructo-2-ki nase activity elicited by phorbol 12,13-dibutyrate was blocked by cycl oheximide. In contrast, the effect of insulin did not require protein synthesis. This study demonstrates that different mitogenic signal tra nsduction pathways control the levels of fructose 2,6-bisphosphate. Th e high rate of glycolysis in proliferating Swiss 3T3 cells may be expl ained by an increase in the levels of this regulatory metabolite. (C) 1994 Academic Press, Inc.