Complexity in O-linked oligosaccharide biosynthesis engendered by multiple polypeptide N-acetylgalactosaminyltransferases
Complexity in O-linked oligosaccharide biosynthesis engendered by multiple polypeptide N-acetylgalactosaminyltransferases
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DOI：
10.1093/glycob/6.7.701
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发表时间：
1996-10-01
期刊：
影响因子：
4.3
通讯作者：
Marth, JD
中科院分区：
文献类型：
--
作者：
Marth, JD
N-乙酰半乳糖胺（GalNAc）与丝氨酸和苏氨酸的羟基在肽背景下的连接启动脊椎动物O-糖基化的产生，尽管参与这种翻译后修饰的组分的身份、特异性和位置一直存在争议。Robert Hill等人的研究发现，O-糖基化开始于高尔基体的一个或多个隔室（汉诺威等人，1982;埃尔哈默和科恩菲尔德，1984;罗斯，1984;阿贝琼和赫希伯格，1987; Deschuyteneer等人，1988;皮勒等人，1990;罗斯等人，1994;施韦泽等人，1994）。虽然使用了各种细胞类型，但其他人已经表明内质网是O-糖生物合成的位点（Strous，1979; Cummings等，1983; Patzelt和Weber，1986; Perez-Vilar等，1991; Ellinger和Pavelka，1992）。尽管可能有相当数量的实验室是错误的，但是，由于O-聚糖生物合成中的复杂性来源，所有实验室都可能是正确的，这些不同的结果是以前没有定义的。尽管已经注意到相邻带电残基的负面影响以及相邻脯氨酸、丝氨酸和苏氨酸残基的频率增加（Hill等，1977; O 'Connell等，1991，1992; Wilson等，1991; Wang等，1992，1993; Elhammer等，1993; Nehrke等，1996）。然而，对O-聚糖序列的一些调查已经导致报告了O-糖基化位点的预测，成功率约为78-88%（Elhammer et al，1993; Chou et al，1995）。脊椎动物来源的多肽（pp）GalNAc-转移酶活性的纯化和表征为解决这些问题提供了材料（Hagopian和Eylar，1969; Sugiura等人，1982; Elhammer和Kornfeld，1986; Wang等人，1992），最近的体外研究表明，使用高度纯化的牛GalNAc转移酶，（O 'Connell等，1992; Wang等，1992，1993）。这些数据支持了Robert Hill等人提出的观点，即可能存在多种ppGalNAc转移酶，它们可能独立地起作用以控制脊椎动物细胞中的O-聚糖产生。下面描述的最近的实验现在已经证实了这一生物化学预测，揭示了在脊椎动物基因组内编码多种ppGalNAc转移酶，从而表明
Linkage of JV-acetylgalactosamine (GalNAc) to the hydroxyl group of serine and threonine in a peptide context initiates the production of vertebrate O-glycosylation, although the identity, specificity and location of components involved in this posttranslational modification have been debated. Studies by Robert Hill and others have found that O-glycosylation begins in one or more compartments of the Golgi apparatus (Hanover et al, 1982; Elhammer and Kornfeld, 1984; Roth, 1984; Abeijon and Hirschberg, 1987; Deschuyteneer et al, 1988; Piller et al, 1990; Roth et al, 1994; Schweizer et al, 1994). While various cell types were used, others have indicated that the endoplasmic reticulum is the site of O-glycari biosynthesis (Strous, 1979; Cummings et al, 1983; Patzelt and Weber, 1986; Perez-Vilar et al, 1991; Ellinger and Pavelka, 1992). Although it is possible that a significant number of laboratories are in error, alternatively, all may be correct with these differing results due to a source of complexity in O-glycan biosynthesis not previously defined.In efforts to determine a sequence motif directing O-linked oligosaccharide formation, no consensus signal has emerged, although a negative influence of adjacent charged residues has been noted as well as the enhanced frequency of adjacent proline, serine, and threonine residues (Hill et al, 1977; O'Connell et al, 1991, 1992; Wilson et al, 1991; Wang et al, 1992, 1993; Elhammer et al, 1993; Nehrke et al, 1996). However, some surveys of O-glycan sequences have led to the reported prediction of O-glycosylation sites with approximately 78-88% success (Elhammer et al, 1993; Chou et al, 1995). Purification and characterization of polypeptide (pp) GalNAc-transferase activity from vertebrate sources has provided material to address such issues (Hagopian and Eylar, 1969; Sugiura et al, 1982; Elhammer and Kornfeld, 1986; Wang et al, 1992), and recent studies in vitro have indicated a surprisingly strong preference for threonine residues using highly purified bovine GalNAc transferase (O'Connell et al, 1992; Wang et al, 1992, 1993). These data have supported the view proposed by Robert Hill and others that multiple ppGalNAc-transferases may exist that might act independently to control O-glycan production in vertebrate cells. Recent experiments described below have now confirmed this biochemical prediction, revealing that multiple ppGalNAc-transferases are encoded within the vertebrate genome and thus indicating