BIOSYNTHESIS AND FUNCTION OF GLYCOSPHINGOLIPIDS AND OTHER GLYCOCONJUGATES

神经节苷脂似乎是细胞膜上重要的识别分子。 细胞表面，并已被牵连作为受体的某些 细菌毒素和病毒。 然而，人们对 正常的生理作用。 我们用了B或者装订 作为表面GM 1的特异性探针。 的 多价的B亚基的唯一已知功能是 与GM 1的寡糖链结合。 静态曝光 细胞与B亚基的结合导致增殖反应。 在 相反，生长中的细胞暴露于B亚基会导致 抑制细胞生长。 大鼠胶质瘤C6细胞， 而不受B亚基的影响。 当外源性GM 1 结合到他们的质膜，细胞是结合到他们的细胞膜。 B亚基，其生长受到抑制。 因此，神经节苷脂 是生长调节信号的双峰膜转导器。 各种癌基因转化的NIH 3 T3细胞表现出减少 复杂的神经节苷脂。 当它们的生长受到 二丁酰环磷酸腺苷，神经节苷脂含量增加 表达，进一步支持神经节苷脂之间的关系 和细胞生长。 此外，ras癌基因转化的细胞 显示改变的是磷脂代谢。 相比 正常细胞或被ras原癌基因转化的细胞， 前细胞不分解磷脂酰肌醇二磷酸， 肌醇三磷酸和二酰基甘油。 这些细胞对氟化铝有反应，表明调节性 G蛋白/磷脂酶C复合物无缺陷。 抑制 细胞生长与二丁酰环磷酸腺苷不能恢复 反应 因此，对生长因子的反应丧失不是由于 细胞的生长状态。

Gangliosides appear to be important recognition molecules on the cell surface and have been implicated as receptors for certain bacterial toxins and viruses. Little is known, however, about their normal physiological roles(s). We used the B or binding subunit of cholera toxin as a specific probe for surface GM1. The only known function of the B subunit, which is multivalent, is to bind to the oligosaccharide chain of GM1. Exposure of quiescent cells to the B subunit results in a proliferative response. In contrast, exposure of growing cells to the B subunit leads to an inhibition of cell growth. Rat glioma C6 cells which are deficient in GM1 are not affected by the B subunit. When exogenous GM1 is incorporated into their plasma membranes, the cells are to bind the B subunit and their growth is inhibited. Thus, gangliosides appear to be bimodal membrane transducters of growth regulatory signals. NIH 3T3 cells transformed by various oncogenes exhibit a reduction in complex gangliosides. When their growth is inhibited by dibutyryl cyclic AMP, there is and increase in ganglioside expression, further supporting a relationship between gangliosides and cell growth. In addition, cells transformed by ras oncogenes display alterations is phospholipid metabolism. In contrast to normal cells or cells transformed by a ras proto-oncogene, the former cells do not breakdown phosphatidylinositol-bisphosphate to inositol trisphophate and diacylglycerol upon serum stimulation. The cells do respond to aluminum fluoride indicating the regulatory G protein/phospholipase C complex was not defective. Inhibition of cell growth with dibutyryl cyclic AMP does not restore the response. Thus, loss of response to growth factors is not due to the growth state of the cells.