Disease relevance of B3GAT1

• We suggest, therefore, that the increase in CD57(+) HIV-specific CD8(+) T cells results from chronic antigen stimulation that is a hallmark of HIV infection [1].
• We overexpressed and purified the recombinant human GlcAT-P from Escherichia coli [2].
• Therefore, NCAM isoforms that lack the HNK-1 epitope might play a role in the organ specific metastatic behavior of uveal melanomas [3].
• In liver metastases HNK-1 immunoreactivity was significantly (P = .005) less frequently expressed than NCAM [3].
• Furthermore, a significant decrease of CD8+ CD57+ T cells was found in patients with advanced gastric cancer [4].

Psychiatry related information on B3GAT1

• DESIGN AND SUBJECTS: A 5-h oral glucose tolerance test was performed on 27 healthy volunteers representing two preproNPY genotypes (Leu7/Pro7 and Leu7/Leu7) matched for age, sex, body mass index and physical activity [5].
• Response to therapy was accompanied by an increase in the CD57 lymphocyte subset in one patient, whereas recurrent hallucinations were associated with persistently low CD57 levels in the other case [6].

High impact information on B3GAT1

• We report here evidence that a marker for natural killer (NK) cells, anti-Leu-7 (HNK-1), specifically binds to components of human and rodent central nervous tissue as well as peripheral nervous tissue, especially to myelin sheaths [7].
• Surface expression of CD45RO, CD27, and CD57 on responding cells was used to classify CD4(+) T cell maturation [8].
• However, in contrast to NK cells, they did not express killer inhibitory receptors, CD16, CD56, or CD57 [9].
• The HNK-1 antibody known to define a subpopulation of human lymphocytes with natural killer and killer cell activities was shown to detect a common neuroectodermal antigen [10].
• At 2200 h each day measurements were taken of total leukocytes (WBC), monocytes, granulocytes, lymphocytes, eosinophils, erythrocytes (RBC), B and T lymphocyte subsets, activated T cells, and natural killer (NK) subpopulations (CD56/CD8 dual-positive cells, CD16-positive cells, CD57-positive cells) [11].

Chemical compound and disease context of B3GAT1

• HGF/NK1 was expressed in Escherichia coli and purified to homogeneity using heparin-affinity and fast protein liquid cation-exchange chromatography [12].
• Monoclonal antibodies 10C5 and 11B5, which were raised to human melanoma cells, as well as HNK-1 bind to this glycoprotein [13].
• Substance P activates responses correlated with tumour growth in human glioma cell lines bearing tachykinin NK1 receptors [14].
• The immunosuppressive cyclic undecapeptide, cyclosporin A, inhibited the binding of [125I]substance P to tachykinin NK1 receptors expressed by human IM-9 lymphoblastoid cells, U-373 MG human astrocytoma cells and guinea pig lung parenchyma with IC50 values of 425 +/- 58, 783 +/- 180, and 784 +/- 163 nM respectively [15].
• The glycosylation of Bowes melanoma tissue plasminogen activator: lectin mapping, reaction with anti-L2/HNK-1 antibodies and the presence of sulphated/glucuronic acid containing glycans [16].

Biological context of B3GAT1

• This leads us to the hypothesis that polymorphic or other variation of the 11q telomere may affect the activity of B3GAT1 and be a risk factor for schizophrenia and related psychoses in the general population [17].
• Mice deleted for the B3GAT1 gene show defects in hippocampal long-term potentiation and in spatial memory formation [17].
• Our data unequivocally establish that inflammatory cytokines, particularly TNF-alpha, stimulate the glucuronosyltransferse, GlcAT-P, and GlcAT-S, gene expression in brain endothelial cells and promote T-cell adhesion via SGPG-L-selectin recognition, a preliminary step for onset of neuroinflammation [18].
• The HNK-1 carbohydrate epitope is found in various neural cell adhesion molecules [19].
• Comparative analyses of the enzymatic activities of GlcAT-S and GlcAT-P showed that there are notable differences in the acceptor substrate specificities of these enzymes [19].

Anatomical context of B3GAT1

• Furthermore, CD57 expression on CD8(+) T cells, CD4(+) T cells, and NK cells is a general marker of proliferative inability, a history of more cell divisions, and short telomeres [1].
• Several cell lines expressed high levels of the leukocyte antigen Leu-7 (HNK-1) but were negative for NCAM antigen and mRNA, indicating that the Leu-7 antigen is distinct from NCAM [20].
• Expression of killer cell lectin-like receptor G1 on antigen-specific human CD8+ T lymphocytes during active, latent, and resolved infection and its relation with CD57 [21].
• Nevertheless, the transfection of the GlcAT-I cDNA into COS-1 cells induced the significant expression of the HNK-1 epitope [22].
• Similar co-localisation of CgA and CD57 was found in non-neoplastic Kultschitski cells of the mucosa of small intestine [23].

Associations of B3GAT1 with chemical compounds

• In addition, Val320, which is located on the C-terminal long loop of the neighboring molecule in the dimer and critical in the recognition of the acceptor sugar molecule by the GlcAT-P dimer, is an alanine in GlcAT-S [19].
• Phe245, one of the most important GlcAT-P residues for the recognition of acceptors, is a tryptophan in GlcAT-S [19].
• Interleukin 6 (IL-6) is endowed with a lectin activity for oligosaccharide ligands possessing the HNK-1 epitope (3-sulfated glucuronic acid) found on some mammalian glycoprotein N-glycans (Cebo, C., Dambrouck, T., Maes, E., Laden, C., Strecker, G., Michalski, J. C., and Zanetta, J. P. (2001) J. Biol. Chem. 276, 5685-5691) [24].
• Expression cloning of a human sulfotransferase that directs the synthesis of the HNK-1 glycan on the neural cell adhesion molecule and glycolipids [25].
• Subsequently, we determined the first x-ray crystal structures of human GlcAT-P, in the absence and presence of a donor substrate product UDP, catalytic Mn(2+), and an acceptor substrate analogue N-acetyllactosamine (Galbeta1-4GlcNAc) or an asparagine-linked biantennary nonasaccharide [2].

Physical interactions of B3GAT1

• The monoclonal antibody HNK-1 binds to a carbohydrate determinant in the myelin-associated glycoprotein (MAG) and other glycoproteins of human peripheral nerve [26].
• Electron microscopic analysis of rotary shadowed complexes of laminin-1 and a HNK-1 neoglycoprotein revealed a major binding site on the G domain that comprises the C-terminal globule of the laminin alpha1 chain [27].

Regulatory relationships of B3GAT1

• The transfected Lec2-NCAM cells expressing the HNK-1 glycan were enriched by fluorescence-activated cell sorting [25].
• HGF/NK1 is inefficient at promoting autophosphorylation of the HGF receptor, although some activity was detected at very high concentrations [12].
• These data support the existence, also in human U373 MG cells, of a septide-sensitive NK1 receptor subtype(s) and/or epitope(s) blocked with high affinity by NK1 antagonist [28].
• Further we show that Bowes t-PA expresses glucuronic acid/sulphate containing N-linked glycans and is recognized by anti-carbohydrate L2/HNK-1 monoclonal antibodies [16].
• However, there was no change of the local background incidence of epiblastic HNK-1 positivity in the structure of streaks induced by "activin only" grafts [29].

Other interactions of B3GAT1

• Furthermore, N-CAM 180 did not carry the HNK-1 epitope, whereas the other two isoforms did [30].
• We further observed that CD8(+) cells expressing CD57, a marker of replicative senescence, also expressed KLRG1; however, a population of CD57(-)KLRG1(+) cells was also identified [21].
• The results combined together indicate that the cloned HNK-1ST directs the synthesis of the HNK-1 carbohydrate epitope on both glycoproteins and glycolipids in the nervous tissues [25].
• A comparison of the GlcAT-I with another beta1,3-glucuronyltransferase involved in the HNK-1 epitope biosynthesis revealed that the two beta1,3-glucuronyltransferases exhibited distinct and no overlapping acceptor substrate specificities in vitro [22].
• Thirty-seven carcinoids of the gastrointestinal tract were studied with immunohistochemical staining for chromogranin A (CgA) and Leu-7 (CD57) [23].

Analytical, diagnostic and therapeutic context of B3GAT1

• Northern blot analysis indicated that human GlcAT-P is expressed mainly in the brain [31].
• Selected 5 tumors from this group were studied in detail using confocal laser scanning microscopy (CLSM) and double immunofluorescence staining to disclose the patterns of distribution of CgA and CD57 positive granules within the individual tumor cells [23].
• Different patterns of chromogranin A and Leu-7 (CD57) expression in gastrointestinal carcinoids: immunohistochemical and confocal laser scanning microscopy study [23].
• In this study, bone marrow biopsy specimens from 36 patients with T-cell GLL and from 25 control patients with cytopenias and relative or absolute increases in blood large granular lymphocytes were studied by immunohistochemistry using antibodies to the cytolytic lymphocyte antigens CD8, CD56, CD57, TIA-1, and granzyme B [32].
• Western blot analysis of prostate extracts showed that monoclonal antibodies TURP-27 and HNK-1 bound glycoproteins with molecular weights of 180,000, 140,000, 120,000, 100,000, 90,000, and 69,000 [33].

References