GLYCOPROTEIN IN HORMONE OLIGOSACCHARIDES

描述：以序列S04-终止的N-连接低聚糖 4-GalNAc-beta1，4GlcNAc-beta(SGN)在糖蛋白上是保守的 从鱼类到哺乳动物的脊椎动物的激素。这意味着 它们具有非常重要的功能，其定义是一个长期目标 申请者的研究成果。这些寡糖结构是 被SGN特异性受体识别，并在 例如，活体在调节黄体生成素循环半衰期以最大化其 排卵周期中受体的激活。高度监管的 这些结构的合成产生了一族低聚糖 含有由蛋白质启动的GalNAc-Beta1，4-GlcNAc-beta序列 所选糖蛋白上特异的β1，4GalNAc转移酶。三 通过随后添加S04可以产生不同的家庭成员， 唾液酸，或岩藻糖，由蛋白质无关的转移酶，如 GalNAc-4-磺酸转移酶。该项目将追求两个主要的具体 目标：1)。蛋白质调控的分子基础的定义-- β1糖基化的特定和蛋白质非依赖性形式， 4体内外GalNAc-T和GalNAc-SulfoT，2)。 蛋白质特异性结构特征的分子定义 β1，4GalNAc转移酶与非蛋白质依赖性GalNAc-4-SulfoT 这解释了他们的性质以及这与监管的关系 他们的表情。这些独特的合成之间的关系 低聚糖的结构及其在体内的生物学作用 使用引入蛋白质特异的β1的构建体确定， 4将GalNAcT识别决定簇转化为另一种蛋白质。的特点 蛋白质特异的β1，4GalNAcT和非蛋白质依赖性的GalNAc-4- 通过克隆这些转移酶，将在分子水平上定义SulfoT 并确定他们的结构特征与他们的能力之间的关系 选择性地修饰低聚糖。 申请者将特别强调发展的 转移酶的表达调控。了解精选的 具有特定寡糖结构的糖蛋白的修饰 将提供有关生殖关键过程的重要信息 生物学，以及恶性转化、炎症、细胞 识别和蛋白质靶向。

DESCRIPTION: N-linked oligosaccharides terminating with the sequence S04- 4-GalNAc-beta1, 4GlcNAc-beta (SGN) have been conserved on the glycoprotein hormones of vertebrate species from fish to mammals. This implies that they serve highly important functions whose definition is a long term goal of the applicant's research. These oligosaccharide structures are recognized by an SGN-specific receptor, and play an essential role in vivo, for example, in regulating LH circulating half life to maximize its receptor activation during the ovulatory cycle. The highly regulated synthesis of these structures yields a family of oligosaccharides containing the sequence GalNAc-beta1, 4-GlcNAc-beta initiated by protein specific beta1, 4GalNAc transferase on selected glycoproteins. Three distinct family members can be produced by the subsequent addition of S04, sialic acid, or fucose by protein-independent transferases such as the GalNAc-4-sulfo transferase. This project will pursue two major specific aims: 1). A definition of the molecular basis for regulation of protein- specific and protein-independent forms of glycosylation by the beta1, 4GalNAc-T and the GalNAc-sulfoT in vitro and in vivo, and 2). Molecular definition of the structural features of the protein specific beta1, 4GalNAc transferase and the protein independent GalNAc-4-sulfoT that account for their properties and how this relates to the regulation of their expression. Relationships between the synthesis of these unique oligosaccharide structures and their biological role in vivo will be determined using constructs that introduce the protein-specific beta1, 4GalNAcT recognition determinant into another protein. Characteristic of the protein-specific beta1, 4GalNAcT and the protein independent GalNAc-4- sulfoT will be defined at molecular level, by cloning these transferases and establishing how their structural features related to their ability to selectively modify oligosaccharides. The applicant will place particular emphasis on the developmental regulation of transferase expression. Understanding the selective modification of glycoproteins with specific oligosaccharide structures will provide important information on processes central to reproductive biology, as well as malignant transformation, inflammation, cell recognition, and protein targeting.