Kuge O, Nishijima M, Akamatsu Y
Department of Chemistry, National Institute of Health, Tokyo, Japan.
J Biol Chem. 1991 Apr 5;266(10):6370-6.
A phosphatidylserine-auxotrophic mutant of cultured Chinese hamster ovary cells, PSA-3, manifests a defect in phosphatidylserine synthase I activity (Kuge, O., Nishijima, M., and Akamatsu, Y. (1986) J. Biol. Chem. 261, 5790-5794). We cloned a Chinese hamster gene, designated pssC, which was able to transform the PSA-3 cell line to a phosphatidylserine prototroph. The resultant transformant contained phosphatidylserine in normal amounts but remained defective in phosphatidylserine synthase I activity, indicating that pssC is a suppressor gene. Using the genomic fragment of pssC as a probe, a cDNA clone of pssC was isolated, and its nucleotide sequence was determined. A computer search through a protein data bank revealed that pssC had homology with the Escherichia coli psd gene encoding the proenzyme of phosphatidylserine decarboxylase at the amino acid level. Introduction of the cloned pssC gene into PSA-3 resulted in a 2-fold increase in phosphatidylserine decarboxylase activity. When the pssC cDNA was placed downstream of the yeast GAL1 promoter and introduced into yeast Saccharomyces cerevisiae cells, the phosphatidylserine decarboxylase activity increased in a galactose-dependent manner. These results indicate that pssC encodes phosphatidylserine decarboxylase. The mechanism by which pssC complements the defect of PSA-3 in phosphatidylserine biosynthesis is discussed.
培养的中国仓鼠卵巢细胞的磷脂酰丝氨酸营养缺陷型突变体PSA-3,在磷脂酰丝氨酸合酶I活性方面表现出缺陷(久下,O.,西岛,M.,和赤松,Y.(1986年)《生物化学杂志》261,5790 - 5794)。我们克隆了一个中国仓鼠基因,命名为pssC,它能够将PSA-3细胞系转化为磷脂酰丝氨酸原养型。所得转化体含有正常量的磷脂酰丝氨酸,但在磷脂酰丝氨酸合酶I活性方面仍有缺陷,表明pssC是一个抑制基因。使用pssC的基因组片段作为探针,分离出了pssC的cDNA克隆,并确定了其核苷酸序列。通过蛋白质数据库进行计算机搜索发现,pssC在氨基酸水平上与编码磷脂酰丝氨酸脱羧酶原酶的大肠杆菌psd基因具有同源性。将克隆的pssC基因导入PSA-3后,磷脂酰丝氨酸脱羧酶活性增加了2倍。当pssC cDNA置于酵母GAL1启动子下游并导入酿酒酵母细胞时,磷脂酰丝氨酸脱羧酶活性以半乳糖依赖的方式增加。这些结果表明pssC编码磷脂酰丝氨酸脱羧酶。本文讨论了pssC弥补PSA-3在磷脂酰丝氨酸生物合成中缺陷的机制。