Protein kinase C-dependent regulation of human erythroleukemia (HEL) cell sphingosine kinase activity
Protein kinase C-dependent regulation of human erythroleukemia (HEL) cell sphingosine kinase activity
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DOI：
10.1016/0005-2760(96)00092-6
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发表时间：
1996-10-18
期刊：
影响因子：
--
通讯作者：
Bell, RM
中科院分区：
文献类型：
--
作者：
Buehrer, BM;Bardes, ES;Bell, RM
鞘氨醇激酶既参与鞘氨醇的分解代谢，又参与鞘氨醇-l-磷酸的信号转导途径。本文研究了几种生物活性药物对人红细胞白血病（HEL）细胞鞘氨醇激酶活性的调节作用。用phorbol 12-肉豆汁酸13-乙酸酯（PMA）处理HEL细胞可引起鞘氨醇激酶活性的时间和浓度依赖性增加，鞘氨醇激酶活性以phorbol酯和二酰基甘油特异性方式增加。蛋白激酶C （PKC）抑制剂Staurosorine和calphostin C阻断了鞘氨醇激酶活性的增加，表明PMA对鞘氨醇激酶的作用依赖于PKC的转录和翻译。纯化的PKC对鞘氨醇激酶活性无直接影响。然而，这些研究发现，磷脂酰丝氨酸在体外刺激HEL细胞鞘氨酸激酶活性。有趣的是，其他HEL细胞分化诱导剂二甲亚砜和维甲酸对鞘氨醇激酶活性没有影响。这些结果表明了pkc依赖性鞘氨醇激酶激活的一个独立而独特的途径，并提示鞘氨醇激酶在调节细胞功能中的作用。
Sphingosine kinase functions in both the catabolism of sphingosine and in signal transduction pathways utilizing sphingosine-l-phosphate, The regulation of sphingosine kinase activity in human erythroleukemia (HEL) cells was investigated by treatment with several bioactive agents. Treatment of HEL cells with phorbol 12-myristate 13-acetate (PMA) caused a time- and concentration- dependent increase in sphingosine kinase activity measured in vitro, Sphingosine kinase activity increased in a phorbol ester- and diacylglycerol-specific manner. Staurosorine and calphostin C, protein kinase C (PKC) inhibitors, blocked the increase in sphingosine kinase activity, suggesting a PKC-dependent regulation, The effects of PMA on sphingosine kinase were dependent on transcription and translation. Purified PKC had no direct effect on sphingosine kinase activity. However, these studies led to the observation that HEL cell sphingosine kinase activity is stimulated in vitro by phosphatidylserine. Interestingly, other inducers of HEL cell differentiation, dimethylsulfoxide and retinoic acid, did not affect sphingosine kinase activity. These results indicate a separate and distinct pathway of PKC-dependent sphingosine kinase activation, and suggest a role for sphingosine kinase in regulation of cell function.