Chen C, Fenderson B A, Andrews P W, Hakomori S
Fred Hutchinson Cancer Research Center, University of Washington, Seattle 98104.
Biochemistry. 1989 Mar 7;28(5):2229-38. doi: 10.1021/bi00431a039.
Retinoic acid induced differentiation of TERA-2-derived human embryonal carcinoma cells is accompanied by a dramatic reduction of extended globo-series glycolipids, including galactosyl globoside, sialylgalactosyl globoside, and globo-A antigen (each recognized by specific MoAbs). Associated with these glycolipid changes, the activities of two key enzymes, alpha 1----4 galactosyltransferase (for synthesis of globotriaosyl core structure) and beta 1----3 galactosyltransferase (for synthesis of galactosyl globoside), were found to be reduced 3- to 4-fold. The latter enzyme plays a key role in the synthesis of extended globo-series structures, and its characterization has not been reported previously. Therefore, its catalytic activity was studied in detail, including substrate specificity, detergent and phospholipid effects, pH and cation requirements, and apparent Km. During retinoic acid induced differentiation, a series of Lex glycolipid antigens (recognized by anti-SSEA-1 antibody) and their core structures (lacto-series type 2 chains) increase dramatically. In parallel with these changes in glycolipid expression, the activities of two key enzymes, beta 1----3 N-acetylglucosaminyltransferase (for extension of lacto-series type 2 chain) and alpha 1----3 fucosyltransferase (for synthesis of Lex structure), were found to increase by 4- and 2-fold, respectively. Similarly, an increase in the expression of several gangliosides (e.g., GD3 and GT3) during retinoic acid induced differentiation was mirrored by a 4-fold increase in the activity of alpha 2----3 sialyltransferase (for synthesis of ganglio core structure, GM3). The results suggest a coordinate regulation of key glycosyltransferases involved in core structure assembly and terminal chain modification.(ABSTRACT TRUNCATED AT 250 WORDS)
视黄酸诱导TERA - 2来源的人胚胎癌细胞分化，伴随着包括半乳糖基球蛋白、唾液酸半乳糖基球蛋白和球A抗原（每种均由特异性单克隆抗体识别）在内的延伸球系列糖脂显著减少。与这些糖脂变化相关的是，两种关键酶——α1→4半乳糖基转移酶（用于合成球三糖核心结构）和β1→3半乳糖基转移酶（用于合成半乳糖基球蛋白）的活性降低了3至4倍。后一种酶在延伸球系列结构的合成中起关键作用，此前尚未见其特性报道。因此，对其催化活性进行了详细研究，包括底物特异性、去污剂和磷脂效应、pH和阳离子需求以及表观Km。在视黄酸诱导分化过程中，一系列Lex糖脂抗原（由抗SSEA - 1抗体识别）及其核心结构（乳糖系列2型链）显著增加。与这些糖脂表达变化同时，两种关键酶——β1→3 N - 乙酰葡糖胺基转移酶（用于延伸乳糖系列2型链）和α1→3岩藻糖基转移酶（用于合成Lex结构）的活性分别增加了4倍和2倍。同样，视黄酸诱导分化过程中几种神经节苷脂（如GD3和GT3）表达的增加，与α2→3唾液酸转移酶（用于合成神经节核心结构GM3）活性增加4倍相对应。结果表明参与核心结构组装和末端链修饰的关键糖基转移酶存在协同调节。（摘要截短于250字）
