ACTIVATION OF SPHINGOSINE KINASE IN PHEOCHROMOCYTOMA PC12 NEURONAL CELLS IN RESPONSE TO TROPHIC FACTORS

Nerve growth factor (NGF), basic fibroblast growth factor (bFGF), dibu tyryl cAMP and forskolin, known differentiating agents for pheochromoc ytoma PC12 cells, induced sustained activation of sphingosine kinase, the enzyme responsible for the formation of the sphingolipid second me ssenger, sphingosine-l-phosphate, which mediates the mitogenic effects of certain growth factors, In contrast, epidermal growth factor and i nsulin-like growth factor-1, which stimulate proliferation of PC12 cel ls, induced only small and transient increases in sphingosine kinase a ctivity, Of the growth factors examined, NGF was the most potent activ ator of sphingosine kinase, inducing a 4-fold increase in V-max. Sphin gosine kinase activity induced by NGF, but not FGF, was blocked by the protein kinase inhibitor K252a when added simultaneously, with minima l effect when added after 60 min, Thus, activation of sphingosine kina se may have an important role in neural differentiation. (C) 1997 Fede ration of European Biochemical Societies.