Studies on the significance of bioactive gangliosides in cellular growth and differntiation.

细胞表面的碳水化合物识别在细胞间的相互作用、细胞的生长和分化过程中起着重要的作用，到目前为止，大多数这样的调节潜力都是在唾液酸化的神经节苷脂家族上报道的，使用外源添加这些糖脂的培养细胞系统。我们之前曾报道，二唾液酸神经节苷脂GD3强烈促进培养的肾上皮细胞(MDCK)中的离子和水的运输。在大鼠胚胎成纤维细胞3Y1中观察到新的、特异的GD3的出现，这些细胞被DNA病毒来源的不同癌基因(腺病毒E1A、SV40-T和myc)转导。抗GD3的单抗可逆地抑制这些细胞的生长。GD3在处于增殖状态的神经元和神经胶质细胞中显著升高。最近，我们发现四唾液酸神经节苷脂G1b可以特异性地促进人神经母细胞瘤细胞的分化，导致神经发生的促进，并且当G1b和ATP加入细胞中时，G1b特异性地刺激同一细胞的几个细胞表面蛋白的磷酸化。结果表明，这种细胞表面蛋白的磷酸化可能是通过特定神经节苷脂特异性激活的独特的细胞表膜蛋白激酶(S)(ECTO-GG激酶)来实现的。抑制这种磷酸化导致抑制G1b依赖的促进神经发生，强烈提示这两个细胞事件之间的相互关系与一个新的生物信号转导系统--ECTO生物信号转导系统的出现。

Carbohydrate recognition at cell surface is known to importantly be involved in cell to cell interactions, cell growth and differentiation.Most of such modulatory potentials have so far been reported on a family of sialylated glycosphingolipids, gangliosides, using cultured cell system added with these glycolipids exogenously. We previously reported that a disialoganglioside GD3 strongly promotes ions and water transport in cultured kidney epithelial cells (MDCK). Newly and specific appearance of GD3 was observed in rat embryonic fibroblastic cells, 3Y1, which were transfected and transformed with various oncogenes of DNA-virus origin (adenovirus E1A, SV40-T and myc). The monoclonal antibody to GD3 reversibly inhibits cell growth of these cells. The remarkable elevation of GD3 was reported on neuron and glial cells in their proliferative states. More recently we have found that a tetrasialoganglioside G 1b specifically can promote differentiation of the human neuroblastoma cells, leading to the promotion of neuritogenesis and also that G 1b specifically stimulates the phosphorylation of several cell surface proteins of the same cells, when the G 1b and ATP are added to the cells. The results indicate that this cell surface protein phosphorylation might be carried out by unique cell surface membrane protein kinase(s) (ecto-Gg kinase) which is specifically activated by a particular ganglioside. Inhibition of this phosphorylation resulted in the inhibition of G 1b-dependent promotion of neuritogenesis, strongly suggesting the interrelationship between those two cell events and occurrence of a new biosignal transduction, ecto biosignal transduction system.