Glycobiology, 2001, Vol. 11, No. 7 515-522
© 2001 Oxford University Press
Epidermal growth factor receptor glycosylation is required for ganglioside GM3 binding and GM3-mediated suppresion of activation
2Department of Pediatrics, Children’s Memorial Hospital, Institute for Education and Research, Northwestern University Medical School, 2300 Children’s Plaza, Chicago, IL 60614, USA, 3Department of Dermatology, Children’s Memorial Hospital, Institute for Education and Research, Northwestern University Medical School, 2300 Children’s Plaza, Chicago, IL 60615, USA, and 4Department of Tumor Immunology, Tokyo Metropolitan Institute of Medical Science, Honkomagome, Bunkyo-ku, Tokyo, Japan
Gangliosides are able to bind to the epidermal growth factor receptor and inhibit its activation, but the mechanism of this inhibition is unknown. To address the role of receptor carbohydrates in facilitating interaction with gangliosides, we examined the ability of GM3 to bind the deglycosylated receptor and inhibit its autophosphorylation. Flow cytometry studies demonstrated that deglycosylation of the receptor did not affect its ability to be transported to the cell membrane. In contrast with the native (fully glycosylated) receptor, GM3 did not coimmunoprecipitate with the deglycosylated receptor. Using a novel colorimetric bead binding assay, GM3 was shown to bind well to the immunoprecipitated native receptor but not at all to the deglycosylated receptor. Finally, the addition of GM3 to cells with deglycosylated epidermal growth factor receptors did not result in significant further inhibition of autophosphorylation of the receptor, despite a 10-fold decrease in phosphorylation of the native epidermal growth factor receptor by 200 µM GM3. These studies suggest that ganglioside affects epidermal growth factor receptor activity through a direct interaction that requires receptor glycosylation, and contribute to our understanding of the role of gangliosides in cell membrane function.
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