Activation of sphingosine kinase in pheochromocytoma PC12 neuronal cells in response to trophic factors

FEBS Letters

Edsall, Lisa C¹  Rius, Ricardo A¹  Spiegel, Sarah¹ 

[1] Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, 353 Basic Science Building, 3900 Reservoir Road NW, Washington, DC 20007, USA

关键词: Nerve growth factor;    Neurotrophic factor;    PC12 cell;    Sphingosine kinase;    trkA;    SPP;    sphingosine-1-phosphate;    cAMP;    dibutyryl cAMP;    PBS;    phosphate-buffered saline;    TLC;    thin layer chromatography;    NGF;    nerve growth factor;    bFGF;    basic fibroblast growth factor;    EGF;    epidermal growth factor;    IGF-1;    insulin-like growth factor-1;   

DOI  :  10.1016/S0014-5793(97)01277-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 V _max. 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.

【 授权许可】

Unknown