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.