Gersten K M, Natsuka S, Trinchera M, Petryniak B, Kelly R J, Hiraiwa N, Jenkins N A, Gilbert D J, Copeland N G, Lowe J B
Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor 48109-0650, USA.
J Biol Chem. 1995 Oct 20;270(42):25047-56. doi: 10.1074/jbc.270.42.25047.
Terminal Fuc alpha 1-3GlcNAc moieties are displayed by mammalian cell surface glycoconjugates in a tissue-specific manner. These oligosaccharides participate in selectin-dependent leukocyte adhesion and have been implicated in adhesive events during murine embryogenesis. Other functions for these molecules remain to be defined, as do the tissue-specific expression patterns of the corresponding alpha-(1-3)-fucosyltransferase (alpha 1-3FT) genes. This report characterizes a murine alpha 1-3FT that shares 77% amino acid sequence identity with human ELAM ligand fucosyltransferase (ELFT, also termed Fuc-TIV). The corresponding gene maps to mouse chromosome 9 in a region of homology with the Fuc-TIV locus on human chromosome 11q. In vitro, the murine alpha 1-3FT can efficiently fucosylate the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc (apparent Km of 0.71 mM) to form an unusual tetrasaccharide (Gal alpha 1-3Gal beta 1-4[Fuc alpha 1-3]GlcNAc) described in periimplantation mouse tissues. The enzyme can also form the Lewis x determinant from Gal beta 1-4GlcNAc (Km = 2.05 mM), and the sialyl Lewis x determinant from NeuNAc alpha 2-3Gal beta 1-4GlcNAc (Km = 1.78mM). However, it does not yield sialyl Lewis x determinants when expressed in a mammalian cell line that maintains sialyl Lewis x precursors. Transcripts from this gene accumulate to low levels in hematopoietic organs, but are unexpectedly abundant in epithelia that line the stomach, small intestine, colon, and epididymus. Epithelial cell-specific expression of this gene suggests function(s) in addition to, and distinct from, its proposed role in selectin ligand synthesis.
末端岩藻糖α1-3GlcNAc部分以组织特异性方式由哺乳动物细胞表面糖缀合物展示。这些寡糖参与选择素依赖性白细胞黏附,并与小鼠胚胎发生过程中的黏附事件有关。这些分子的其他功能以及相应的α-(1-3)-岩藻糖基转移酶(α1-3FT)基因的组织特异性表达模式仍有待确定。本报告描述了一种小鼠α1-3FT,它与人类ELAM配体岩藻糖基转移酶(ELFT,也称为Fuc-TIV)具有77%的氨基酸序列同一性。相应的基因定位于小鼠9号染色体上与人类11号染色体q上Fuc-TIV基因座同源的区域。在体外,小鼠α1-3FT可以有效地将三糖Galα1-3Galβ1-4GlcNAc(表观Km为0.71 mM)岩藻糖基化,形成在植入前小鼠组织中描述的一种不寻常的四糖(Galα1-3Galβ1-4[Fucα1-3]GlcNAc)。该酶还可以从Galβ1-4GlcNAc(Km = 2.05 mM)形成Lewis x决定簇,从NeuNAcα2-3Galβ1-4GlcNAc(Km = 1.78 mM)形成唾液酸化Lewis x决定簇。然而,当在维持唾液酸化Lewis x前体的哺乳动物细胞系中表达时,它不会产生唾液酸化Lewis x决定簇。该基因的转录本在造血器官中积累到低水平,但在胃、小肠、结肠和附睾内衬的上皮细胞中意外丰富。该基因在上皮细胞中的特异性表达表明,除了其在选择素配体合成中所提出的作用外,还具有其他功能,且这些功能与之不同。