Modulation of epidermal growth factor receptor phosphorylation by endogenously expressed gangliosides

The effect of changing the ganglioside composition of Chinese hamster ovary K1 cells on the function of the epidermal growth factor receptor (EGFr) wa s examined by studying the signalling pathway generated after the binding o f epidermal growth factor (EGF) both in cells depleted of glycosphingolipid s by inhibiting glucosylceramide synthase activity and in cell lines expres sing different gangliosides as the result of stable transfection of appropr iate ganglioside glycosyl transferases. After stimulation with EGF, cells d epleted of glycolipids showed EGFr phosphorylation and extracellular signal -regulated protein kinase 2 (ERK2) activity as parental cells expressing GM 3 [ganglioside nomenclature follows Svennerholm (1963) J. Neurochem. 10, 61 3-623] or as transfected cells expressing mostly GM2 and GD1a as the result of stable transfection of UDP-GalNAc :LacCer/GM3/GD3 N-acetylgalactosaminy l-transferase. However, cells stably transfected with CMP-NeuAc:GM3 sialylt ransferase and expressing GD3 at the cell surface showed both decreased EGF r phosphorylation and ERK2 activation after stimulation with EGF. Results s uggest that changes in the ganglioside composition of cell membranes might be important in the regulation of the EGF signal transduction.