Molecular cloning of a cDNA encoding a novel human leukocyte alpha-1,3-fucosyltransferase capable of synthesizing the sialyl Lewis x determinant.
Molecular cloning of a cDNA encoding a novel human leukocyte alpha-1,3-fucosyltransferase capable of synthesizing the sialyl Lewis x determinant.
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发表时间：
1994-06
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通讯作者：
S. Natsuka;K. M. Gersten;K. Zenita;R. Kannagi;J. Lowe
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作者：
S. Natsuka;K. M. Gersten;K. Zenita;R. Kannagi;J. Lowe
sialyl Lewis x决定因子（NeuAc α 2,3 gal β 1,4 [Fuc α 1,3]GlcNAc）是e -选择素和p -选择素的白细胞反受体的重要组成部分。唾液酰Lewis x合成的最后一步是由作用于唾液酰化糖缀合前体的α -1,3-聚焦转移酶催化。培养的人白细胞细胞系表达α -1,3-聚焦转移酶基因Fuc-TIV或ELFT，但不表达其他三个克隆的人α -1,3-聚焦转移酶基因。然而，fu - tiv /ELFT在sialyl Lewis x生物合成中的生理作用尚不确定，因为它可以在一些（但不是全部）转染细胞系中催化该决定因素的合成，其方式取决于宿主细胞的糖基化表型。我们在此报道了一种编码新的人类白细胞α -1,3-聚焦转移酶的cDNA的分子克隆，称为Fuc-TVII，能够合成唾液酰基Lewis x片段。cDNA序列预测了一个341个氨基酸长的II型跨膜蛋白，是典型的哺乳动物糖基转移酶。当在哺乳动物细胞中表达时，fucl - tvii cDNA指导细胞表面唾液刘易斯x片段的合成，但不指导刘易斯x、刘易斯a、唾液刘易斯a或VIM-2决定因子的合成。fu - tvii在体外能有效利用α -2,3-唾液基乳胺形成唾液基Lewis x四糖，但不利用乳糖胺形成Lewis x片段。Northern blot分析显示，fucc - tvii基因在HL-60细胞（人早幼粒细胞细胞系）和YT细胞（自然杀伤细胞样细胞系）中均有转录。Fuc-TVII是一种白细胞α -1,3-聚焦基转移酶，通过催化唾液Lewis x决定因子的合成参与选择素配体的合成。
The sialyl Lewis x determinant (NeuAc alpha 2,3Gal beta 1, 4[Fuc alpha 1,3]GlcNAc) is an essential component of leukocyte counterreceptors for E-selectin and P-selectin. The final step in sialyl Lewis x synthesis is catalyzed by alpha-1,3-fucosyltransferases acting on sialylated glycoconjugate precursors. Cultured human leukocytic cell lines express an alpha-1,3-fucosyltransferase gene termed Fuc-TIV or ELFT but do not express the other three cloned human alpha-1,3-fucosyltransferase genes to any significant degree. The physiological role of Fuc-TIV/ELFT in sialyl Lewis x biosynthesis is uncertain, however, since it can catalyze the synthesis of this determinant in some, but not all, transfected cell lines in a manner that is dependent upon the glycosylation phenotype of the host cell. We report here the molecular cloning of a cDNA encoding a new human leukocyte alpha-1,3-fucosyltransferase, termed Fuc-TVII, capable of synthesizing the sialyl Lewis x moiety. The cDNA sequence predicts a 341-amino acid-long type II transmembrane protein typical of mammalian glycosyltransferases. When expressed in mammalian cells, the Fuc-TVII cDNA directs the synthesis of cell surface sialyl Lewis x moieties but not the Lewis x, Lewis a, sialyl Lewis a, or VIM-2 determinants. Fuc-TVII can efficiently utilize alpha-2,3-sialyllactosamine in vitro to form the sialyl Lewis x tetrasaccharide but does not utilize lactosamine to form the Lewis x moiety. Northern blot analyses show that the Fuc-TVII gene is transcribed in HL-60 cells, a human promyelocytic cell line, and in YT cells, a natural killer-like cell line. Fuc-TVII represents a leukocytic alpha-1,3-fucosyltransferase that can participate in selectin ligand synthesis via its ability to catalyze the synthesis of sialyl Lewis x determinants.