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Signal Transduction of Bioactive Carbohydrate Chains and Their Genetic Expression

生物活性碳水化合物链的信号转导及其基因表达

基本信息

批准号：
01440091
负责人：
NAGAI Yoshitaka
金额：
$ 11.9万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

During the period of investigation on the mechanism of signal transduction through carbohydrate chain and of the gene-expression, the following findings were obtained ;1 Membrane-associated glycoproteins which were characteristically phoshporylated in response with GQlb ganglioside were found in human neuroblastoma cells, whose neurite was extended with GQlb ganglioside. These kinases were inhibited with an impermeable inhibitor for protein kinase, which was also inhibited the activity of GQlb-mediated neurite outgrowth of the cells. The results indicate an occurrence of carbohydrate chain dependent signal transduction system.2 By gene-transfection technique, the characteristic expression of glycosphingolipids, such as GD3 by adenovirus ElA and myc, and lacto-and ganglio-series glycolipids by src, fes, fps and ras oncogenes, were observed in rat 3Yl cells, indicating that the different oncogene products modify the glycolipid metabolism in their own manners.3 When compared the proliferative and the secretory phases of human uterine endometrium, a characteristic induction of sulfatide was observed in the secretory phase. Since the ganglioside contents in both phases were identical each other, a ngative charge due to the sulfate group was added in the secretory phase, in which the fertilized egg was trapped and embedded. Probably, the sulfotransferase activity for the synthesis of sulfatide is induced by progesterone.4 N-(O-linoleoyl) hydroxy fatty acyl sphingosyl glucose was found to be characteristically contained in mammalian epidermis and showed an activity enhancing the kerachinization process of kerachinocytes established from fetal rat skin. The activity involved the stimulation of cornified envelops-formation and the activation of glutamyl peptide transglutaminase and was found to be the same activity as that induced by phorbol ester.

在研究糖链信号转导机制和基因表达机制的过程中，获得了以下结果：1在用GQ 1b神经节苷脂延长神经突的人神经母细胞瘤细胞中，发现了响应GQ 1b神经节苷脂的特征性磷酸化的膜相关糖蛋白。这些激酶被蛋白激酶的不可渗透的抑制剂抑制，其也抑制了GQlb介导的细胞的神经突生长的活性。结果表明，糖链依赖的信号转导系统的存在。2通过基因转染技术，在大鼠3 Y1细胞中观察到特征性的鞘糖脂表达，如腺病毒ElA和myc表达的GD 3，以及src、fes、fps和ras癌基因表达的乳糖和神经节糖脂。表明不同的癌基因产物以它们自己的方式改变糖脂代谢。3当比较人子宫内膜的增殖期和分泌期时，在分泌期观察到硫苷脂的特征性诱导。由于在两个阶段的神经节苷脂含量是相同的，负电荷由于硫酸基团被添加在分泌期，受精卵被捕获和嵌入。很可能，硫苷脂合成的磺基转移酶活性是由胆甾酮诱导的。4 N-（O-亚油酰基）羟基脂肪酰基鞘糖葡萄糖被发现是特征性地包含在哺乳动物表皮中，并显示出活性增强角质化过程的角质细胞建立从胎鼠皮肤。该活性涉及刺激角质化包膜形成和激活谷氨酰肽转谷氨酰胺酶，并且发现与佛波酯诱导的活性相同。