Inhibition of thrombin-stimulated cell proliferation by ceramide is not through inhibition of extracellular signal-regulated protein kinase.
Inhibition of thrombin-stimulated cell proliferation by ceramide is not through inhibition of extracellular signal-regulated protein kinase.
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神经酰胺对凝血酶刺激的细胞增殖的抑制并非通过抑制细胞外信号调节蛋白激酶。
DOI：
10.1006/bbrc.1997.7669
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Williamson,JR
中科院分区：
文献类型：
--
作者：
Guo,YL;Peng,M;Kang,B;Williamson,JR
凝血酶受体的激活在CCL 39细胞中提供了强的促有丝分裂信号。神经酰胺被发现抑制凝血酶介导的有丝分裂在这些细胞中，而二氢神经酰胺没有效果。许多生长抑制剂通过抑制细胞外信号调节激酶（ERK）信号通路发挥作用。然而，无论是神经酰胺，也不dihydroceramide阻断凝血酶诱导的ERK激活。相反，这两种药物增强ERK活性。凝血酶刺激ERK下游的c-fos、c-jun和cyclin D1的表达，但神经酰胺或二氢神经酰胺对这种刺激没有影响。因此，在CCL 39细胞中，神经酰胺对凝血酶刺激的细胞生长的抑制似乎不是通过对ERK活化的影响介导的。此外，这些数据还表明，神经酰胺对凝血酶刺激的细胞生长和ERK活性的单独作用是由不同的机制介导的。
Activation of the thrombin receptor provides a strong mitogenic signal in CCL39 cells. Ceramide was found to inhibit thrombin-mediated mitogenesis in these cells while dihydroceramide had no effect. Many growth inhibitors exert their effect by inhibiting extracellular signal-regulated kinase (ERK) signaling pathway. However, neither ceramide nor dihyroceramide blocked the thrombin-induced activation of ERK. In contrast, both agents potentiated ERK activity. The expression of c-fos, c-jun and cyclin D1, which are downstream of ERK in the mitogenic pathway were stimulated by thrombin but this stimulation was not affected by ceramide or dihydroceramide. Therefore, the ceramide inhibition of thrombin-stimulated cell growth in CCL39 cells does not appear to be mediated by an effect on the activation of ERK. Furthermore, the data also suggest that the separate effects of ceramide on thrombin-stimulated cell growth and ERK activity are mediated by different mechanisms.