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，并已被牵连为受体 某些细菌毒素和病毒。然而，人们对此知之甚少 关于这些质膜的正常生理作用(S) 组件。探讨表面神经节苷脂在细胞中的作用 生长时，我们使用霍乱毒素的B或结合亚基作为 表面GM1专用探头。唯一已知的功能是 B亚基是多价的，它与寡糖结合 GM1链。静态大鼠胸腺细胞和小鼠胸腺细胞的暴露 3T3细胞对B亚基的增殖反应为 通过增加DNA合成和细胞数量来衡量。B类 亚基增强了其他有丝分裂原的作用，如 表皮生长因子、胰岛素和血清。作为有丝分裂原 通过几种跨膜信号调节它们的作用 系统和诱导原癌基因的早期表达 C-myc和c-fos，B亚基启动它们的能力 对早期促分裂反应进行了研究。唯一的急性反应 B辐射对胸腺细胞和3T3细胞的影响 亚单位，是细胞内游离钙离子的快速上升， 依赖于细胞外钙离子的存在。根本没有 CAMP、肌醇磷酸盐或细胞内pH升高，或 腺苷环化酶或蛋白激酶C的激活。 亚基还可诱导c-myc和c-fos的表达。虽然 B亚基触发快速增加的机制 细胞内游离钙离子与原癌基因的诱导 表达式尚不清楚，它必须通过其特定的 与细胞表面的GM1结合。因此，神经节苷脂可能会发挥作用 作为调节细胞的信号的膜传感器的作用 成长。

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 know, however, about the normal physiological role(s) of these plasma membrane components. To explore the role of surface gangliosides in cell growth, 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 rat thymocytes and mouse 3T3 cells to the B subunit resulted in a proliferative response as measured by increased DNA synthesis and cell numbers. The B subunit potentiated the effects of other mitogens such as epidermal growth factor, insulin and serum. As mitogens mediate their effects through several transmembrane signalling systems and induce the early expression of the proto-oncogenes c-myc and c-fos, the ability of the B subunit to initiate these early mitogenic responses was explored. The only acute response observed in both thymocytes and 3T3 cells exposed to the B subunit, was a rapid rise in intracellular free Ca2+ which depended on the presence of extracellular Ca2+. There was no elevation of cAMP, inositol phosphates, or intracellular pH, or activation of adenylate cyclase or protein kinase C. The B subunit also induced expression of c-myc and c-fos. Although the mechanism by which the B subunit triggers a rapid increase in intracellular free Ca2+ and induction of proto-oncogene expression is not yet known, it must be through its specific binding to GM1 on the cell surface. Thus, gangliosides may play a role as membrane transducers of signals that regulate cell growth.