Gangliosides are sialic acid containing glycosphingolipids and are primarily localized at the cell surface. Upon oncogenic transformation of cells in vivo and in vitro, there are changes in the chemical composition of gangliosides and their organization. The significance of these changes is essentially unknown. Indirect evidence, however, has suggested the possibility that these glycolipid changes may inhibit cell adhesion and disrupt normal cellular recognition. Recent experiments have suggested a possible correlation between transformation sensitive ganglioside changes and the function of polypeptide growth factors. The overall aim of this proposal is to study the influence of glycosphingolipids on growth factor receptors both in vitro and in intact cells. Specifically, the aims of this proposal are to: 1.) Examine the effects of glycosphingolipids and phospholipids on the purified epidermal growth factor receptor. 2.) Discriminate between the lipid effects of EGF binding and receptor associated kinase activities. 3.) Examine the effects of glycosphingolipids or growth factor stimulated tyrosine phosphylation in intact cells. 4.) Examine the effects of anti-glycosphingolipid antibodies on the binding and kinase activities of growth factor receptors. The knowledge of glycosphingolipid effects on growth factor receptors may eventually fill the gap in understanding the role of glycosphingolipids in cell growth control and transformation. Changes in the composition or expression of glycosphingolipids caused by various oncogenic transformants may result in the loss of regulation of growth factor receptors and thus contribute to the aberrant growth behavior of transformed cells.
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