GD3 synthase gene expression in PC12 cells results in the continuous activation of TrkA and ERK1/2 and enhanced proliferation
GD3 synthase gene expression in PC12 cells results in the continuous activation of TrkA and ERK1/2 and enhanced proliferation
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DOI：
10.1074/jbc.275.8.5832
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发表时间：
2000-02-25
影响因子：
4.8
通讯作者：
Furukawa, K
中科院分区：
文献类型：
--
作者：
Fukumoto, S;Mutoh, T;Furukawa, K
转染神经节苷脂GD 3合成酶基因的大鼠嗜铬细胞瘤细胞系（PC 12）显示出神经节苷脂谱的显着变化和增强的增殖和神经突起延伸神经生长因子（NGF）刺激无反应。在这些转染细胞中，观察到TrkA的连续磷酸化和ERK 1/2的激活而没有NGF处理。用激酶抑制剂如除莠霉素A、K-252 a和PD 98059进行的增殖抑制实验表明，增强的增殖实际上是由于Ras/MEK/ERK通路的激活。通过免疫印迹和交联技术检测到在GD 3合成酶转染细胞中存在TrkA二聚体，而无论是否经NGF处理，这些转染细胞中GD 1b和GT 1b的表达增加可能导致TrkA构象变化，形成二聚体并被持续激活，这些结果可能表明神经节苷脂在生理和恶性过程中对细胞增殖的调节作用。
A rat pheochromocytoma cell line (PC12) transfected with ganglioside GD3 synthase gene showed a marked change in the ganglioside profile and enhanced proliferation and no response of neurite extension to nerve growth factor (NGF) stimulation. In these transfectant cells, a continuous phosphorylation of TrkA and the activation of ERK1/2 without NGF treatment were observed. Proliferation inhibition experiments with kinase inhibitors such as herbimycin A, K-252a, and PD98059 revealed that the enhanced proliferation was actually due to the activation of the Ras/MEK/ERK pathway. A TrkA dimer was detected in the GD3 synthase transfectant cells regardless of NGF treatment by crosslinking and immunoblotting, The increased expression of GD1b and GT1b in these transfectant cells might induce the conformational change of TrkA to form a dimer and to be activated continuously, These results may indicate regulatory roles of gangliosides in cell proliferation under physiological and malignant processes.