GD3 synthase gene expression in PC12 cells results in the continuous activation of TrkA and ERK1/2 and enhanced proliferation |
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Authors: | Fukumoto S Mutoh T Hasegawa T Miyazaki H Okada M Goto G Furukawa K Urano T |
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Institution: | Department of Biochemistry II, Nagoya University School of Medicine, Nagoya 466-0065, Japan. |
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Abstract: | 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 cross-linking 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. |
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