A SINGLE MUTATION AFFECTS BOTH N-ACETYLGLUCOSAMINYLTRANSFERASE AND GLUCURONOSYLTRANSFERASE ACTIVITIES IN A CHINESE-HAMSTER OVARY CELL MUTANT DEFECTIVE IN HEPARAN-SULFATE BIOSYNTHESIS

A SINGLE MUTATION AFFECTS BOTH N-ACETYLGLUCOSAMINYLTRANSFERASE AND GLUCURONOSYLTRANSFERASE ACTIVITIES IN A CHINESE-HAMSTER OVARY CELL MUTANT DEFECTIVE IN HEPARAN-SULFATE BIOSYNTHESIS
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DOI:
10.1073/pnas.89.6.2267
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发表时间:
1992-03-15
影响因子:
11.1
通讯作者:
ESKO, JD
ESKO, JD
中科院分区:
综合性期刊1区
文献类型:
--
作者:
LIDHOLT, K;WEINKE, JL;ESKO, JD

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中国仓鼠卵巢细胞的突变株被发现不再产生硫酸乙酰肝素。对其中一个突变体pgsD-677的鉴定表明,它同时缺乏N-乙酰氨基葡萄糖转移酶和葡萄糖醛酸基转移酶,这两种酶是硫酸乙酰肝素链聚合所必需的。PgsD-677还积累了比野生型多3到4倍的硫酸软骨素。PGSD-677和野生型的细胞杂交细胞恢复了转移酶活性和合成硫酸乙酰肝素的能力。其中一个杂交种的两个分离物表达了双酶缺乏、硫酸乙酰肝素合成缺乏和硫酸软骨素积累增强,这表明所有的性状都是遗传连锁的。这些发现表明,pgsD基因座可能代表了参与糖胺多糖形成协调控制的基因。
Mutants of Chinese hamster ovary cells have been found that no longer produce heparan sulfate. Characterization of one of the mutants, pgsD-677, showed that it lacks both N-acetylglucosaminyl- and glucuronosyltransferase, enzymes required for the polymerization of heparan sulfate chains. pgsD-677 also accumulates 3- to 4-fold more chondroitin sulfate than the wild type. Cell hybrids derived from pgsD-677 and wild type regained both transferase activities and the capacity to synthesize heparan sulfate. Two segregants from one of the hybrids reexpressed the dual enzyme deficiency, the lack of heparan sulfate synthesis, and the enhanced accumulation of chondroitin sulfate, suggesting that all of the traits were genetically linked. These findings indicate that the pgsD locus may represent a gene involved in the coordinate control of glycosaminoglycan formation.