神经节苷脂作为细胞生长的双功能调节剂。
Gangliosides as bimodal regulators of cell growth.
作者信息
Spiegel S, Fishman P H
出版信息
Proc Natl Acad Sci U S A. 1987 Jan;84(1):141-5. doi: 10.1073/pnas.84.1.141.
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.
霍乱毒素的B亚基可特异性结合细胞表面的几种神经节苷脂分子，即半乳糖基-（β1→3）-N-乙酰半乳糖胺基（β1→4）-[N-乙酰神经氨酸（α2→3）]-半乳糖基（β1→4）葡萄糖基（β1→1）神经酰胺（GM1），它能以剂量依赖的方式刺激静止的、未转化的小鼠3T3细胞中的DNA合成和细胞分裂。此外，B亚基增强了3T3细胞对其他有丝分裂原的反应，如表皮生长因子、血小板衍生生长因子和胰岛素。这种协同效应表明，B亚基的作用与这些生长因子中的任何一种都不完全相同，但可能调节了对细胞增殖至关重要的共同效应系统。与之形成鲜明对比的是，B亚基抑制了ras转化的3T3细胞以及快速分裂的正常3T3细胞的生长。因此，相同的细胞根据其生长状态对B亚基表现出双峰反应。我们得出结论，内源性神经节苷脂可能是细胞生长正负信号的双峰调节因子。
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