REGULATED SYNTHESIS OF SIALYLTRANSFERASES

已经确定，糖蛋白的正确糖基化和 糖脂是正常发育和维持高血糖的基础。 动物 然而，对于其结构和功能知之甚少。 寡糖链的相互关系及其调控 表情 在构成碳水化合物链的糖中，唾液酸 酸，仅作为末端糖存在，可能是最广泛的， 虽然不完全，研究。 这是本项目的长远目标 来阐明决定组织和发育的途径 唾液酸部分对糖缀合物的特异性。 至少五个，最有可能更多，唾液酸转移酶是必需的， 哺乳动物中发现的主要唾液酸键的生物合成 糖蛋白 然而，先前对唾液酸功能性的分析 酸和唾液酸转移酶的调节表达受到阻碍 由于缺乏序列信息，因此可以从其中 构建了 这个实验室和其他实验室的努力导致了 肝β-半乳糖苷α 2，6- 唾液酸转移酶mRNA通过糖皮质激素途径调节。 该实验室目前的观察还发现了一个家族， 与肝α 2，6-唾液酸转移酶mRNA密切相关的转录物 并表现出组织特异性表达模式。 至少其中一个 相关的转录本pupp 3编码不同的多肽序列。 本研究的一个直接目标是详细描述 这个家庭的不同成员和关系的评估， 个体转录本的遗传起源。 随后 功能以及在体内和体外模式的合成， 这些转录物和多肽将被处理。 一个平行的目标， 这项研究是阐明的调节途径，支配 该家族的唾液酸转移酶相关转录物的表达。 本 最后，必要的调控序列将被鉴定和测试， 嵌合构建体的表达。

It is well established that correct glycosylation of glycoproteins and glycolipids is fundamental to normal development and maintenance of higher animals. However, little is known about the structural and functional relationship of the oligosaccharide chains and the regulation of their expression. Among the sugars that comprise the carbohydrate chains, sialic acid, present only as the terminal sugars, is perhaps the most extensively, albeit incompletely, studied. It is the long ranged goal of this project to elucidate the pathways that determine the tissue and development specificities of sialic acid moieties on glycoconjugates. At least five, and most likely more, sialytransferases are required in the biosynthesis of the major sialic acid linkages found in mammalian glycoproteins. However, previous analysis of the functionality of sialic acids and the regulated expression of sialytransferases has been hampered by lack of sequence information from which specific molecular probes can be constructed. Efforts from this and other laboratories resulted in the sequence elucidation of the hepatic beta-galactoside alpha2,6- sialytransferase mRNA is modulated via the glucocorticoid pathway. Current observations from this laboratory has also uncovered a family of transcripts closely related to the hepatic alpha2,6-sialytransferase mRNA and exhibit a tissue specific pattern of expression. At least on of these related transcripts putatively encodes a divergent polypeptide sequence. An immediate objective of this study is a detailed characterization of the different members of this family and an assessment of the relationship and genetic origin of the individual transcripts. Subsequently, the functionality as well as in vivo and in vitro patterns of synthesis of these transcripts and polypeptides will be addressed. A parallel goal of this study is the elucidation of regulatory pathways that govern the expression of this family of sialytransferase related transcripts. To this end, requisite regulatory sequences will be identified and tested by the expression of chimeric constructs.