Gangliosides as bimodal regulators of cell growth.
The B subunit of cholera toxin, which binds specifically to several molecules of ganglioside galactosyl-(beta 1----3)-N-acetylgalactosyminyl(beta 1----4)-[N- acetylneuraminyl(alpha 2----3)]-galactosyl(beta 1----4)glucosyl(beta 1----1) ceramide (GM1) on the cell surface, stimulated DNA synthesis and cell division in quiescent, nontransformed mouse 3T3 cells in a dose-dependent manner. In addition, the B subunit potentiated the response of the 3T3 cells to other mitogens, such as epidermal growth factor, platelet-derived growth factor, and insulin. This synergistic effect indicates that the B subunit does not act identically to any of these growth factors but probably modulates a common effector system crucial for cell proliferation. In distinct contrast, the B subunit inhibited the growth of ras-transformed 3T3 cells as well as rapidly dividing normal 3T3 cells. Thus, the same cells, depending on their state of growth, exhibited a bimodal response to the B subunit. We conclude that endogenous gangliosides may be bimodal regulators of positive and negative signals for cell growth.
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects*; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005732:Gangliosides / Q000502:physiology*; D006133:Growth Substances / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D046911:Macromolecular Substances; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009857:Oncogenes
D005732:Gangliosides; D006133:Growth Substances; D007328:Insulin; D046911:Macromolecular Substances; D004815:Epidermal Growth Factor; D002772:Cholera Toxin