Human α1–3 fucosyltransferases

Macher, Bruce A.; Holmes, Eric H.; Swiedler, Stuart J.; Stults, Cheryl L. M.; Srnka, Cheryl A.

doi:10.1093/glycob/1.6.577

Cited by 84 publications

(29 citation statements)

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“…Cell were transfected with 20 g of negative control vector plasmid DNA (pcDNAI) or with the plasmid DNAs pcDNAI-Fuc-TIII, pcDNAIFuc-TVI, or each of the various pcDNAI-Fuc-TCs. Cells were also cotransfected with 1 g of the plasmid pCDM8-CAT (35) Flow Cytometry Analysis-Transfected COS-7 cells were harvested 72 h after transfection and were stained with antibodies diluted in staining media (41), using procedures described previously (6,21,29). Anti-Lewis a and anti-H ascites were used at a dilution of 1:500 and 1:100, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…The total radioactivity in each reaction was determined by subjecting an aliquot to scintillation counting. To assess the amount of radioactive fucose incorporated into product, an additional aliquot was applied to a Dowex 1ϫ2-400 column in the formate form (27)(28)(29)(30). The flow-through fraction plus an additional 2 ml of a water column "wash" was collected, pooled, and subjected to scintillation counting.…”

Section: Methodsmentioning

confidence: 99%

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Human α(1,3/1,4)-Fucosyltransferases Discriminate between Different Oligosaccharide Acceptor Substrates through a Discrete Peptide Fragment

Legault

Kelly

Natsuka

et al. 1995

Journal of Biological Chemistry

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Cell surface ␣(1,3)-and ␣(1,4)-fucosylated oligosaccharides have received a substantial amount of attention because some are thought to be essential to the initiation of immune cell adhesion to vascular endothelium during the inflammatory process (reviewed in Refs. 1-5 and 6 -15). This is perhaps best characterized by the "rolling" type of adhesion mediated by interactions between sialyl Lewis x (sLe x )-bearing glycoconjugates on leukocytes and P-and E-selectin expressed by activated vascular endothelium (5). Animal intervention studies indicate that such fucosylated oligosaccharide molecules can act as anti-inflammatory agents by inhibiting leukocyte-endothelial cell interactions (15-18). Furthermore, absence of such molecules on the leukocytes of individuals with the rare human leukocyte adhesion II syndrome is associated with profound defects in leukocyte-endothelial cell adhesion and with nonpyogenic infections (19,20). These observations suggest that compounds capable of specifically inhibiting leukocyte sialyl Lewis x expression might represent candidates for anti-inflammatory pharmacologic agents.The ␣(1,3)-fucosyltransferases (␣(1,3)-Fuc-Ts) 1 represent a target for such inhibitory agents, since synthesis and expression of the sLe x molecule and related ␣(1,3)-and ␣(1,4)-fucosylated oligosaccharides are controlled, in large measure, by ␣(1,3)Fuc-Ts (5). These enzymes catalyze the attachment of L-fucose in ␣ anomeric linkage to one or more distinct oligosaccharide precursors. Biochemical and molecular cloning studies indicate that the human genome encodes at least five distinct ␣(1,3)-Fuc-Ts (9, 21-28; reviewed in Refs. 5, 29, and 30). Each enzyme can react with one or more structurally distinct oligosaccharides and can thereby generate a unique spectra of cell surface ␣(1,3)-fucosylated oligosaccharide products. In turn, these molecules may exhibit distinct biologic functions, including those involving selectin-dependent cell adhesion.Although the primary sequences are known for several ␣(1,3)-Fuc-Ts (9, 21-28), the structural determinants within these enzymes that dictate their different substrate specificities remain undefined. The purpose of this work is to identify such protein sequence(s) and to provide a conceptual background for work to design or identify molecules that might inhibit ␣(1,3)-Fuc-Ts by interacting with acceptor substrate binding sites.In this study, we chose to explore three human ␣(1,3)-Fuc-Ts (Fuc-TIII, Fuc-TV, and Fuc-TVI) with informative structural and catalytic properties. These enzymes share approximately 85% overall amino acid sequence identity (24,25). The COOH termini of these enzymes maintain nearly identical amino acid sequences, whereas their NH 2 -terminal regions are punctuated by foci of nonidentical amino acids; we term these regions "hypervariable" segments. These three enzymes maintain shared and distinct acceptor substrate specificities. In partic-

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Human α(1,3/1,4)-Fucosyltransferases Discriminate between Different Oligosaccharide Acceptor Substrates through a Discrete Peptide Fragment

Legault

Kelly

Natsuka

et al. 1995

Journal of Biological Chemistry

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“…This mAb recognized the glycoconjugate Lewis y -6/H-5-2 (Le y /H), which shares some structural overlap with sialyl Le x . Le y /H is a selective Ag that is expressed on ECs only in synovium, lymphoid tissues, skin, and thymus as well as on epithelial cells such as keratinocytes (12,14). EC Le y /H expression is up-regulated before the ingress of inflammatory cells in vivo using a cytokine-dependent model of human poison ivy extract-induced contact dermatitis (12).…”

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confidence: 99%

Ley/H: An Endothelial-Selective, Cytokine-Inducible, Angiogenic Mediator

Halloran

Carley

Polverini

et al. 2000

The Journal of Immunology

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Endothelial cells (ECs) are key participants in angiogenic processes that characterize tumor growth, wound repair, and inflammatory diseases, such as human rheumatoid arthritis (RA). We and others have shown that EC molecules, such as soluble E-selectin, mediate angiogenesis. Here we describe an EC molecule, Lewisy-6/H-5-2 glycoconjugate (Ley/H), that shares some structural features with the soluble E-selectin ligand, sialyl Lewisx (sialyl Lex). One of the main previously recognized functions of Lewisy is as a blood group glycoconjugate. Here we show that Ley/H is rapidly cytokine inducible, up-regulated in RA synovial tissue, where it is cell-bound, and up-regulated in the soluble form in angiogenic RA compared with nonangiogenic osteoarthritic joint fluid. Soluble Ley/H also has a novel function, for it is a potent angiogenic mediator in both in vitro and in vivo bioassays. These results suggest a novel paradigm of soluble blood group Ags as mediators of angiogenic responses and suggest new targets for therapy of diseases, such as RA, that are characterized by persistent neovascularization.

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“…The expression of sialyl-Le X , which is one of the physiologically relevant selectin ligands, is controlled by fucosyltransferase FucT-VII during lymphocyte differentiation or activation (33), and core 2 GnT-I, but not GnT-II or GnT-III, is also required to express sialyl-Le X on glycoproteins in human precursor B cells (15). These reports suggest physiological functions for core 2 GnT-I in the immune system.…”

Section: Discussionmentioning

confidence: 94%

The cis-Regulatory Element Gsl5 Is Indispensable for Proximal Straight Tubule Cell-specific Transcription of Core 2 β-1,6-N-Acetylglucosaminyltransferase in the Mouse Kidney

Sekine¹,

Taya²,

Shitara³

et al. 2006

Journal of Biological Chemistry

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Gsl5 regulates the expression of a glycolipid and glycoproteins that contain the Le X epitope in the mouse kidney through tissuespecific transcriptional regulation of the core 2 ␤-1,6-N-acetylglucosaminyltransferase (core 2 GnT) gene. The core 2 GnT gene has six exons and produces three alternatively spliced transcripts. Gsl5 regulates only the expression of the kidney-type mRNA, which is transcribed from the most 5 -upstream exon. By introducing a 159-kb bacterial artificial chromosome (BAC) clone that carries the mouse core 2 GnT gene and its 5 -upstream region into DBA/2 mice that carry a defective Gsl5 allele, we were able to rescue the deficient phenotype. The BAC clone was subsequently engineered to replace the core 2 GnT gene with the sequence of enhanced green fluorescent protein (EGFP) as a reporter by an inducible homologous recombination system in Escherichia coli. The transgenic mice derived from the modified BAC clone expressed EGFP in the kidney, which suggests that the candidate Gsl5 is in the 5 -upstream region of the core 2 GnT gene. Sequence analysis of the 5 -upstream regions of the BAC clone and DBA/2 genomic DNA revealed a candidate sequence for Gsl5 at about 5.5 kb upstream of exon 1. This sequence consisted of eight repeats of two GT-rich units in the wildtype mice, whereas it consisted of only one pair of GT-rich units with a minor modification in the DBA/2 mice. Transgenic mice produced with the EGFP reporter gene construct that included this candidate sequence expressed EGFP exclusively in the proximal straight tubular cells of the kidney. These results indicated that this unique repeat is indeed the Gsl5, and it is a cis-regulatory element responsible for proximal straight tubule cell-specific transcriptional regulation.

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Human α1–3 fucosyltransferases

Cited by 84 publications

References 0 publications

Human α(1,3/1,4)-Fucosyltransferases Discriminate between Different Oligosaccharide Acceptor Substrates through a Discrete Peptide Fragment

Human α(1,3/1,4)-Fucosyltransferases Discriminate between Different Oligosaccharide Acceptor Substrates through a Discrete Peptide Fragment

Ley/H: An Endothelial-Selective, Cytokine-Inducible, Angiogenic Mediator

The cis-Regulatory Element Gsl5 Is Indispensable for Proximal Straight Tubule Cell-specific Transcription of Core 2 β-1,6-N-Acetylglucosaminyltransferase in the Mouse Kidney

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