Studies on the significance of bioactive gangliosides in cellular growth and differntiation.

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Carbohydrate recognition at cell surface is known to importantly be involved in cell to cell interactions, cell growth and differentiation.Most of such modulatory potentials have so far been reported on a family of sialylated glycosphingolipids, gangliosides, using cultured cell system added with these glycolipids exogenously. We previously reported that a disialoganglioside GD3 strongly promotes ions and water transport in cultured kidney epithelial cells (MDCK). Newly and specific appearance of GD3 was observed in rat embryonic fibroblastic cells, 3Y1, which were transfected and transformed with various oncogenes of DNA-virus origin (adenovirus E1A, SV40-T and myc). The monoclonal antibody to GD3 reversibly inhibits cell growth of these cells. The remarkable elevation of GD3 was reported on neuron and glial cells in their proliferative states. More recently we have found that a tetrasialoganglioside G 1b specifically can promote differentiation of the human neuroblastoma cells, leading to the promotion of neuritogenesis and also that G 1b specifically stimulates the phosphorylation of several cell surface proteins of the same cells, when the G 1b and ATP are added to the cells. The results indicate that this cell surface protein phosphorylation might be carried out by unique cell surface membrane protein kinase(s) (ecto-Gg kinase) which is specifically activated by a particular ganglioside. Inhibition of this phosphorylation resulted in the inhibition of G 1b-dependent promotion of neuritogenesis, strongly suggesting the interrelationship between those two cell events and occurrence of a new biosignal transduction, ecto biosignal transduction system.