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.