Extended Core 1 and Core 2 Branched O-Glycans Differentially Modulate Sialyl Lewis x-type L-selectin Ligand Activity*

@article{Mitoma2003ExtendedC1,
  title={Extended Core 1 and Core 2 Branched O-Glycans Differentially Modulate Sialyl Lewis x-type L-selectin Ligand Activity*},
  author={J. Mitoma and B. Petryniak and N. Hiraoka and J. Yeh and J. Lowe and M. Fukuda},
  journal={The Journal of Biological Chemistry},
  year={2003},
  volume={278},
  pages={9953 - 9961}
}
It has been established that sialyl Lewis x in core 2 branched O-glycans serves as an E- and P-selectin ligand. Recently, it was discovered that 6-sulfosialyl Lewis x in extended core 1 O-glycans, NeuNAcα2→3Galβ1→4(Fucα1→3(sulfo→6))GlcNAcβ1→ 3Galβ1→3GalNAcα1→Ser/Thr, functions as an L-selectin ligand in high endothelial venules. Extended core 1O-glycans can be synthesized when a core 1 extension enzyme is present. In this study, we first show that β1,3-N-acetylglucosaminyltransferase-3… Expand
N-glycans of core2 beta(1,6)-N-acetylglucosaminyltransferase-I (C2GnT-I) but not those of alpha(1,3)-fucosyltransferase-VII (FucT-VII) are required for the synthesis of functional P-selectin glycoprotein ligand-1 (PSGL-1): effects on P-, L- and E-selectin binding.
TLDR
A differential functional impact of N-glycosylation on C2GnT-1 and FucT-VII is shown and it is disclosed that a strongly reduced Fuct-VII activity retains the ability to fucosylate PSGL-1 on the core2-based binding site(s) for the three selectins. Expand
Effects of N-glycosylation on the activity and localization of GlcNAc-6-sulfotransferase 1.
TLDR
The sites at which GlcNAc6ST-1 is modified with N-linked glycans and the effects that each glycan has on enzyme activity, specificity, and localization are reported. Expand
Core 2 Branching β1,6-N-Acetylglucosaminyltransferase and High Endothelial Venule-restricted Sulfotransferase Collaboratively Control Lymphocyte Homing*
TLDR
It is suggested that LSST and Core2GlcNAcT cooperatively synthesize HEV-specific L-selectin ligands required for lymphocyte homing and play a critical role in lymphocyte trafficking during chronic inflammation. Expand
Helicobacter pylori β1,3-N-acetylglucosaminyltransferase for versatile synthesis of type 1 and type 2 poly-LacNAcs on N-linked, O-linked and I-antigen glycans.
TLDR
A broader substrate specificity is demonstrated for the H. pylori β3GlcNAcT than previously recognized and its ability as a potent resource for preparative chemo-enzymatic synthesis of complex glycans is demonstrated. Expand
Model Glycosulfopeptides from P-selectin Glycoprotein Ligand-1 Require Tyrosine Sulfation and a Core 2-branched O-Glycan to Bind to L-selectin*
TLDR
It is demonstrated that L-selectin binds with high affinity to the N-terminal region of PSGL-1 through cooperative interactions with three sulfated tyrosine residues and an appropriately positioned C2-O-sLex O-glycan. Expand
Suppression of beta 1,3galactosyltransferase beta 3Gal-T5 in cancer cells reduces sialyl-Lewis a and enhances poly N-acetyllactosamines and sialyl-Lewis x on O-glycans.
TLDR
It is suggested that beta 3Gal-T5 plays a relevant role in gastrointestinal and pancreatic tissues counteracting the glycosylation pattern associated to malignancy, and is necessary for the synthesis and secretion of CA19.9 antigen, whose expression still depends on multiple interacting factors. Expand
Core 1-derived O-glycans are essential E-selectin ligands on neutrophils
TLDR
It is found that E-selectin bound to CD44 and ESL-1 in lysates of T-synthase–deficient neutrophils, and the cells exhibited markedly impaired rolling on E- selectin in vitro and in vivo, failed to activate β2 integrins while rolling, and did not emigrate into inflamed tissues. Expand
High-sensitivity O-glycomic analysis of mice deficient in core 2 {beta}1,6-N-acetylglucosaminyltransferases.
TLDR
Analysis of the C2GnT triple knockout mice revealed a complete loss of both core 2 O-glycans and branched core 1 antennae, confirming that the three known isoenzymes are entirely responsible for producing these structures. Expand
Glycosyltransferases involved in type 1 chain and Lewis antigen biosynthesis exhibit glycan and core chain specificity.
Sialyl Lewis A (SLe(a)), Lewis A (Le(a)), and Lewis B (Le(b)) have been studied in many different biological contexts, for example in microbial adhesion and cancer. Their biosynthesis is complex andExpand
Functional contributions of N- and O-glycans to L-selectin ligands in murine and human lymphoid organs.
TLDR
Cl40 was superior to MECA-79 in blocking lymphocyte-HEV interactions in both wild-type mice and mice deficient in forming O-glycans, and this superiority was more marked in human, as CL40 completely blocked lymphocyte binding to tonsillar HEVs, whereas Meca-79 inhibited only 60%. Expand
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The results obtained clearly indicate that the conversion of C2GnT into a trans-Golgi enzyme resulted in a substantial decrease of core 2 branched oligosaccharides, indicating the critical role of orderly subcellular localization of glycosyltransferases. Expand
A Transfected Sialyltransferase That Is Elevated in Breast Cancer and Localizes to the medial/trans-Golgi Apparatus Inhibits the Development of core-2–based O-Glycans
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The cDNA coding for the human α2,3 SAT tagged with an immunoreactive epitope from the myc gene has been used to map the position of the glycosyltransferase in nontumorigenic and malignant breast epithelial cell lines and demonstrate that the structure of O-glycans synthesized by a cell can be manipulated by transfecting with recombinant gly cosyltransferases. Expand
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Core1-beta 3GlcNAcT and its cognate extended core1 O-glycans are identified as essential participants in the expression of the MECA-79-positive, HEV-specific L-selectin ligands required for lymphocyte homing. Expand
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The structures of the Ser/Thr-linked O-glycans of PSGL-1 synthesized by HL-60 cells metabolically radiolabeled with 3H-sugar precursors are described and demonstrated to be critical for high affinity interactions between PS GL-1 and selectins. Expand
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TLDR
The results indicate that the formation of polylactosaminyl O-glycans and sialyl Le(x) structure in O- glycans is dependent on the core 2 formation. Expand
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