GD3 synthase gene expression in PC12 cells results in the continuous activation of TrkA and ERK1/2 and enhanced proliferation

A rat pheochromocytoma cell line (PC12) transfected with ganglioside GD3 sy nthase 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 herbimy cin A, K-252a, and PD98059 revealed that the enhanced proliferation was act ually due to the activation of the Ras/MEK/ERK pathway. A TrkA dimer was de tected in the GD3 synthase transfectant cells regardless of NGF treatment b y crosslinking and immunoblotting, The increased expression of GD1b and GT1 b in these transfectant cells might induce the conformational change of Trk A to form a dimer and to be activated continuously, These results may indic ate regulatory roles of gangliosides in cell proliferation under physiologi cal and malignant processes.