OLIGOSACCHARIDE STRUCTURE AND FUNCTION IN RECOGNITION

可溶性糖蛋白和膜糖蛋白上的寡糖表现出 巨大的结构多样性，表明它们编码了高度特定的 信息。要做到这一点，必须存在：L)独一无二 低聚糖结构，2)高度特异的糖基转移酶，以及 3)能够识别这些结构的受体并利用它们的 唯一的信息。利用编码信息的生物功能 低聚糖可能主要存在于多细胞中 生物体，包括细胞：细胞识别，细胞：基质 识别以及细胞内和细胞外贩运 糖蛋白。挑战一直是找出那些利用 生物低聚糖中编码的结构信息 目的。我们已经确定了一种主要的新的碳水化合物特异性受体 肝脏中调节循环半衰期的系统，因此， 糖蛋白激素促黄体生成素等的生物活性 含末端SO4-4GalNAc-β，14GlcNAc-Beta1，2man-的糖蛋白 α(S4GGnM)在它们的寡糖上。S4GGnM-末端的合成 结构受到严格的监管，仅在有限的数量上发现 糖蛋白。肝内皮细胞表达500,000个S4GGnM结合 在其表面的位置/细胞。S4OGnM受体是从 并将使用我们已有的方法广泛地表征 为其他碳水化合物特定系统开发。对象的属性 受体将在分离的肝内皮细胞中确定。这个 一级结构将通过cDNA分析来确定。蛋白水解酶 将使用片断和突变来定义所涉及的区域 在配体结合和靶向方面。其他潜在功能将包括 通过使用受体识别其他糖蛋白来建立 S4GGnM-终端结构。在其他组织中表达该受体的细胞 将被鉴定和鉴定以确定受体是否是 一个多基因家族的成员。免疫定位和原位杂交将 用来检测S4GGnM受体表达的调节 新生大鼠胎儿发育、妊娠和性成熟的获得。 由于许多糖蛋白包括膜糖蛋白在正常和 恶性细胞，病毒表面糖蛋白，生长因子 前体、凝血因子、补体成分和激素可能 与其具有巨大潜在关联性的受体系统相互作用 无论是病理状态还是正常状态。

The oligosaccharides on soluble and membrane glycoproteins exhibit tremendous structural diversity, suggesting they encode highly specific information. For this to be the case there must exist: l) Unique oligosaccharide structures, 2) Highly specific glycosyltransferases, and 3) Receptors capable of recognizing these structures and utilizing their unique information. Biologic functions making use of information encoded in oligosaccharides are likely to be manifest primarily in multicellular organisms and include such phenomena as cell:cell recognition, cell:matrix recognition, and both intra- and extra-cellular trafficking of glycoproteins. The challenge has been to identify systems which utilize the structural information encoded in oligosaccharides for a biologic purpose. We have identified a major new carbohydrate-specific receptor system in liver which regulates the circulatory half life and, thereby, the biologic activity of the glycoprotein hormone lutropin and other glycoproteins bearing terminal SO4-4GalNAc-beta, 14GlcNAc-beta1, 2Man- alpha (S4GGnM) on their oligosaccharides. The synthesis of S4GGnM-terminal structures is highly regulated and they are found on only a limited number of glycoproteins. Hepatic endothelial cell express >500,000 S4GGnM-binding sites/cell at their surface. The S4OGnM-receptor has been isolated from rat liver and will be extensively characterized using approaches we have developed for other carbohydrate-specific systems. The properties of the receptor will be defined in isolated hepatic endothelial cells. The primary structure will be determined by cDNA analysis. Proteolytic fragmentation and mutagenesis will be used to define the regions involved in ligand binding and targeting. Additional potential functions will be established by using the receptor to identify other glycoproteins bearing S4GGnM-terminal structures. Cells expressing the receptor in other tissues will be identified and characterized to establish if the receptor is part of a multigene family. Immunolocalization and in situ hybridization will be used to examine the regulation of S4GGnM-receptor expression during fetal development, pregnancy, and gain of sexual maturity in newborn rats. Since many glycoproteins including membrane glycoproteins on normal and malignant cells, surface glycoproteins on viruses, growth factor precursors, coagulation factors, complement components, and hormones may interact with the receptor system it has tremendous potential relevance to both pathologic and normal states.