Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.1.18 (branching enzyme)
 628 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selectins are carbohydrate-binding adhesion molecules that play important roles in control of leukocyte traffic. Glycosyltransferases involved in selectin ligand biosynthesis include the alpha1,3-fucosyltransferases FucT-VII and FucT-IV, one or more sialyltransferases, and at least one O-linked branching enzyme. Previous studies have shown that core 2 beta1-6-N-glucosaminyltransferase (C2GlcNAcT-I; EC 2.4.1.102) is required for functional modification of PSGL-1, the leukocyte P-selectin ligand, but have been ambiguous on whether this enzyme is involved in E-selectin ligand formation. Using an attachment and rolling assay under defined shear flow in vitro, this study shows that C2GlcNAcT-I(-) lymphoid cells stably transfected with FucT-VII complementary DNA attach and roll well on E-selectin at 1.5 dynes/cm.(2) Further, attachment and rolling on P-selectin of neutrophils is sharply reduced and that of short- term polarized Th1 cells is virtually abolished, with leukocytes from C2GlcNAcT-I(-/-) mice. In contrast, both neutrophils and Th1 cells from C2GlcNAcT-I(-/-) mice attach and roll as well as wild-type cells on E-selectin. These results show that C2GlcNAcT-I is selectively required for biosynthesis of ligands for P-selectin, but is not essential for at least some E-selectin ligands. Distinct requirements for C2GlcNAcT-I in the formation of ligands for E-selectin versus P-selectin represents a novel level of regulation of expression of selectin ligands and lymphocyte traffic. (Blood. 2001;97:3806-3811)
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PMID:Differential requirements for the O-linked branching enzyme core 2 beta1-6-N-glucosaminyltransferase in biosynthesis of ligands for E-selectin and P-selectin. 1138 20

Fuc-TIV and Fuc-TVII are the two alpha(1, 3)-fucosyltransferases in myeloid cells responsible for the biosynthesis of sialyl Lewis X (sLe(x)), the minimal ligand structure for the selectins. We have compared the ability of Fuc-TIV and Fuc-TVII to generate sLe(x)-like epitopes in transfected Chinese hamster ovary (CHO)-Pro(-)5 cells expressing the P-selectin glycoprotein ligand-1 and the core-2 branching enzyme C2GnT. We found that mouse Fuc-TIV and Fuc-TVII can generate similar levels of cell surface sLe(x). Surprisingly however, Fuc-TIV-generated sLe(x) was resistant to proteinase K and trypsin treatment and could be removed from cells by delipidation with chloroform/methanol, whereas 80-90% of Fuc-TVII-generated sLe(x) was protease-sensitive, and most of it resistant to delipidation. Despite similar levels of sLe(x) on the cell surface, Fuc-TVII transfectants adhered to immobilized E-selectin-IgG under static and flow conditions better than Fuc-TIV transfectants. Binding was mainly protease sensitive, indicating that glycoproteins were more efficient ligands than glycolipids. In summary, we conclude that the two fucosyltransferases differ in their in vivo specificity for acceptor substrates with Fuc-TVII generating sLe(x) preferentially on glycoproteins, whereas most of the Fuc-TIV-generated sLe(x) is found on glycolipids. Interestingly, the non-catalytic portion of Fuc-TIV in a Fuc-TIV/VII chimeric enzyme mediated the specificity for glycolipid substrates.
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PMID:The alpha (1,3)-fucosyltransferase Fuc-TIV, but not Fuc-TVII, generates sialyl Lewis X-like epitopes preferentially on glycolipids. 1235 18