GLYCOPROTEINS IN NORMAL & LEUKEMIC CELL DIFFERENTIATION

描述：(改编自调查人员的摘要)主要 该提案的目的是确定聚唾液酸在 发展与肿瘤恶性程度，以及各种不同基因的作用 聚唾液酸形成中的2，8-唾液酸基转移酶。调查人员 克隆了编码聚唾液酸基转移酶PST的基因 神经细胞黏附分子N-CAM。他们发现，仅PST就可以增加 所有2，8-连接的唾液酸都是形成聚唾液酸所必需的。通过 利用这个基因，他们还证明了聚唾液酸化的N-CAM 促进轴突生长和分支比单独使用N-CAM要好得多。 此外，他们还发现，聚唾液酸神经节苷脂也可以 由神经节苷脂特异的聚唾液酸转移酶GD3/GT3ST合成。 基于这些发现，提出了四个主要的进一步研究领域 1.阐明α-2，8-唾液酸基转移酶在植物生长发育中的作用 聚唾液酸的形成。这些研究将确定PST和PST的作用 其他α-2，8-唾液酸基转移酶，如STX、ST8SiaIII和GD3/GT3ST 多唾液酸在胚胎发育过程中的形成及其表达。 2.测定聚唾液酸在神经细胞伸展和分化中的作用 肿瘤细胞迁移。3.确定聚唾液酸在体内的作用 胚胎发育。这些研究将确定聚唾液酸的作用 酸在小鼠发育中的异位表达，以及系统和 PST基因的组织特异性敲除。4.一种新型载体的分离 含有聚唾液酸的糖蛋白。这些研究将确定一种 携带聚唾液酸的新型糖蛋白S及其活性测定 在各种组织中表达。这些研究将使调查人员 了解聚唾液酸在发育过程中的生理作用 和致癌作用。

DESCRIPTION: (adapted from the investigator's abstract) The primary objective of the proposal is to determine the roles of polysialic acid in development and tumor malignancy, and the roles of various a2,8-sialyltransferases in polysialic acid formation. The investigators have cloned a cDNA encoding polysialyltransferase, PST, that polysialylates the neural cell adhesion molecule, N-CAM. They found that PST alone can add all a2,8-linked sialic acid necessary for polysialic acid formation. By using this cDNA, they also demonstrated that polysialylated N-CAM facilitates neurite outgrowth and branching much better than N-CAM alone. Furthermore, they have found that polysialylated gangliosides can also be synthesized by a ganglioside-specific polysialyltransferase, GD3/GT3ST. Based on these findings, four major areas of further study are proposed as follows: 1. Elucidation of the roles fo various a2,8-sialyltransferases in polysialic acid formation. The studies will determine the roles of PST and other a2,8-sialyltransferases such as STX, ST8SiaIII and GD3/GT3ST in polysialic acid formation and their expression during embryonic development. 2. Determining the roles of polysialic acid in neural cell extension and tumor cell migration. 3. Determining the roles of polysialic acid in embryonic development. The studies will determine the roles of polysialic acid in mouse development by ectopic expression, and systemic and tissue-specific knock-out of PST gene. 4. Isolation of a novel carrier glycoprotein that contains polysialic acid. The studies will identify a novel glycoprotein(s) that carries polysialic acid and determine its expression in various tissues. These studies will allow the investigators to understand the physiological roles of polysialic acid during development and oncogenesis.