BIOSYNTHESIS AND FUNCTION OF GLYCOSPHINGOLIPIDS AND OTHER GLYCOCONJUGATES

神经节苷脂似乎是重要的识别分子。 细胞表面，并被认为是特定的受体 细菌毒素和病毒。然而，人们对此知之甚少。 他们正常的生理角色(S)。我们使用了B或绑定 霍乱毒素亚单位作为表面GM1的特异性探针。这个 B亚基是多价的，其唯一已知的功能是 结合到GM1的寡糖链上。静止状态的曝光 细胞转到B亚单位会导致增殖反应。在……里面 相比之下，生长细胞暴露于B亚单位会导致 抑制细胞生长。缺失的大鼠脑胶质瘤C6细胞 在GM1中不受B亚基的影响。当外源GM1是 结合到他们的质膜中，细胞将结合 B亚基，其生长受到抑制。因此，神经节苷脂出现了。 成为生长调控信号的双峰膜传感器。 不同癌基因转化的NIH3T3细胞表现出减少 在复杂的神经节苷脂中。当它们的生长被抑制时 二丁酰环磷酸腺苷，神经节苷脂有增加 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 显示的改变是磷脂代谢。与之形成鲜明对比的是 正常细胞或ras原癌基因转化的细胞， 前一种细胞不会分解磷脂酰肌醇-二磷酸 三磷酸肌醇和甘油二酯对血清的刺激作用。 这些细胞确实对氟化铝有反应，这表明 G蛋白/磷脂酶C复合体无缺陷。抑制 二丁酰环AMP对细胞生长的影响不能恢复 回应。因此，对增长因素的反应丧失并不是由于 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.