Activation of sphingosine kinase in pheochromocytoma PC12 neuronal cells in response to trophic factors.
Nerve growth factor (NGF), basic fibroblast growth factor (bFGF), dibutyryl cAMP and forskolin, known differentiating agents for pheochromocytoma PC12 cells, induced sustained activation of sphingosine kinase, the enzyme responsible for the formation of the sphingolipid second messenger, sphingosine-1-phosphate, which mediates the mitogenic effects of certain growth factors. In contrast, epidermal growth factor and insulin-like growth factor-1, which stimulate proliferation of PC12 cells, induced only small and transient increases in sphingosine kinase activity. Of the growth factors examined, NGF was the most potent activator of sphingosine kinase, inducing a 4-fold increase in Vmax. Sphingosine kinase activity induced by NGF, but not FGF, was blocked by the protein kinase inhibitor K252a when added simultaneously, with minimal effect when added after 60 min. Thus, activation of sphingosine kinase may have an important role in neural differentiation.
Rius
R A
RA
Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
Edsall
L C
LC
Spiegel
S
S
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D026121:Indole Alkaloids; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009474:Neurons / Q000201:enzymology; D016716:PC12 Cells; D010673:Pheochromocytoma; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D051381:Rats; D020917:Receptor, trkA; D013997:Time Factors; D000099157:Sphingosine Kinase
D002227:Carbazoles; D002352:Carrier Proteins; D004815:Epidermal Growth Factor; D006133:Growth Substances; D026121:Indole Alkaloids; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D020917:Receptor, trkA; D000099157:Sphingosine Kinase; C049985:staurosporine aglycone