Sphingosine 1-phosphate activates Erk-1/-2 by transactivating epidermal growth factor receptor in rat-2 cells
Sphingosine 1-phosphate activates Erk-1/-2 by transactivating epidermal growth factor receptor in rat-2 cells
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DOI：
10.1080/713803698
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发表时间：
2000-08-01
期刊：
影响因子：
4.6
通讯作者：
Chun, JS
中科院分区：
文献类型：
--
作者：
Kim, JH;Kim, JH;Chun, JS
在1-磷酸鞘氨醇(S1P)刺激的大鼠-2细胞中，我们研究了导致细胞外信号调节蛋白激酶(ERK)1和2激活的信号通路，S1P以剂量依赖的方式瞬时激活ERK-1/-2，其激活可被百日咳毒素、RasN17的表达或抑制Raf或MEK-1/-2阻断，S1P诱导的ERK-L/-2的激活也被特异性抑制剂AG1478抑制表皮生长因子受体酪氨酸激酶的激活所抑制，提示EGF受体酪氨酸激酶的激活参与了这一信号通路。用GF109203X抑制蛋白激酶C(PKC)可使S1P诱导的ERK-1/-2的激活增加2倍，而在无S1P处理的情况下抑制PKC也可激活ERK-1/-2，AG1478可阻断PKC抑制对ERK-1/-2激活的刺激作用，提示PKC参与了EGF受体酪氨酸激酶激活的调节，从而导致ERK-1/-2的激活。综上所述，这些结果表明，S1P通过PKC依赖的途径激活EGF受体，该途径将RAS信号与大鼠2细胞中ERK-1/-2的激活联系起来。
We investigated a signaling pathway leading to activation of extracellular signal-regulated protein kinase (Erk) 1 and 2 in Rat-2 cells stimulated with sphingosine 1-phosphate (S1P), S1P treatment transiently activated Erk-1/-2 in a dose-dependent manner, and its activation was blocked by pertussis toxin, expression of RasN17, or inhibition of Raf or MEK-1/-2, S1P-induced activation of Erk-l/-2 was also suppressed by the inhibition of epidermal growth factor (EGF) receptor tyrosine kinase with the specific inhibitor AG1478, suggesting that activation of EGF receptor tyrosine kinase was involved in the signaling pathway. S1P-induced Erk-1/-2 activation was enhanced up to 2-fold by inhibiting protein kinase C (PKC) with GF109203X, and PKC inhibition in the absence of S1P treatment also activated Erk-1/-2, The stimulatory effects of Erk-1/-2 activation by PKC inhibition was blocked by treating cells with AG1478, suggesting the involvement of PKC in the regulation of EGF receptor tyrosine kinase activation that leads to Erk-1/-2 activation. Together, these results suggest that S1P activates the EGF receptor through a PKC-dependent pathway that links Ras signaling to the activation of Erk-1/-2 in Rat-2 cells.