Disease relevance of Gcnt2

• The cDNA encoding IGnT was isolated from a murine PCC4 teratocarcinoma cDNA library by nucleic acid hybridization using probes generated from the human IGnT cDNA [1].
• IGnT B showed an expression profile closely related to that of IGnT A and was strongly expressed in the liver, kidney and intestine, and moderately in the mammary gland, submaxially gland, embryonic stem cells, and embryonal carcinoma cells [2].
• Transforming growth factor beta up-regulates expression of the N-acetylglucosaminyltransferase V gene in mouse melanoma cells [3].
• Introduction of the beta1-4 N-acetylglucosaminyltransferase (GnT-III) gene was reported to suppress metastasis in highly metastatic B16-hm murine melanoma cells (Yoshimura, M., Nishikawa, A. , Ihara, Y., Taniguchi, S., and Taniguchi, N.(1995) Proc. Natl. Acad. Sci. U. S. A. 92, 8754-8758) [4].
• A mouse lymphoma cell line resistant to the leukoagglutinating lectin from Phaseolus vulgaris is deficient in UDP-GlcNAc: alpha-D-mannoside beta 1,6 N-acetylglucosaminyltransferase [5].

High impact information on Gcnt2

• Malignant transformation of fibroblast and epithelial cells is accompanied by increased beta 1-6 N-acetylglucosaminyltransferase V (GlcNAc-TV) activity, a Golgi N-linked oligosaccharide processing enzyme [6].
• The Mgat1 gene encodes N-acetylglucosaminyltransferase I (Glc-NAc-TI; EC 2.4.1.101), the transferase that initiates the synthesis of complex N-glycans [7].
• Using transfected cell lines, we found that CHO-131 binding required the functional activity of the glycosyltransferases alpha2,3-sialyltransferase, alpha1,3-fucosyltransferase-VII, and core 2 beta1,6 N-acetylglucosaminyltransferase (C2GnT) [8].
• beta 1-4 N-acetylglucosaminyltransferase (GnT-III) catalyzes the formation of bisecting N-acetylglucosamine (GlcNAc) in the biosynthesis of N-linked oligosaccharides [9].
• Overexpression of full-length mouse Large generated functionally glycosylated alpha-DG in Pro(-5) Chinese hamster ovary (CHO) cells, and the amount was increased by co-expression of protein:O-mannosyl N-acetylglucosaminyltransferase 1 [10].

Biological context of Gcnt2

• Core 2 beta1,6-N-acetylglucosaminyltransferase I (C2GnT-I) plays a pivotal role in the biosynthesis of mucin-type O-glycans that serve as ligands in cell adhesion [11].
• Genomic analysis indicated that IGnT A and IGnT B were derived by alternative splicing; the unique portion was encoded by exon 1, and the common portion was encoded by exons 2 and 3 [2].
• A novel form of murine beta-1,6-N:-acetylglucosaminyltransferase that forms branches in poly-N:-acetyllactosamines (designated as IGnT B) was cloned based on sequence homology to the known IGnT (designated as IGnT A) [2].
• The molecular genetics of the mouse I beta-1,6-N-acetylglucosaminyltransferase locus [12].
• Minimal catalytic domain of N-acetylglucosaminyltransferase V [13].

Anatomical context of Gcnt2

• Many selectin ligands require modification of glycoproteins by leukocyte core2 beta1,6-N-acetylglucosaminyltransferase (Core2GlcNAcT-I) [14].
• The results presented demonstrate that IGnT and the I antigen appear in epithelial cells and dividing cells [1].
• N-acetylglucosaminyltransferase V (Mgat5)-mediated N-glycosylation negatively regulates Th1 cytokine production by T cells [15].
• Modification of CD43 and other lymphocyte O-glycoproteins by core 2 N-acetylglucosaminyltransferase [16].
• N-acetylglucosaminyltransferase V activity has been measured under saturating conditions in the extracts of seven cultured cell lines using as substrates, UDP-[3H]-GlcNAc and a synthetic 8-methoxylcarbonyloctyl trisaccharide [17].

Associations of Gcnt2 with chemical compounds

• The only non-conserved residue within the beta1,6-N-acetylglucosaminyltransferase family, Cys235, is also a free thiol in the presence of dithiothreitol; however, in the absence of reductant, Cys235 forms an intermolecular disulfide linkage [11].
• UDP-GlcNAc: Manalpha1-6Manbeta-R beta1-6 N-acetylglucosaminyltransferase V (EC 2.4.1.155, GlcNAc-TV) is a Golgi enzyme that substitutes the trimannosyl core in the biosynthetic pathway for complex-type N-linked glycans [13].
• N-Acetylglucosaminyltransferase V (GlcNAc-T V) is a glycosyltransferase which transfers N-acetylglucosamine in beta(1,6) linkage to the alpha(1,6)-linked mannose residue of Asn-linked oligosaccharides [18].
• An assay for the enzyme responsible for the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins, a UDP-N-acetylglucosamine:peptide N-acetylglucosaminyltransferase, is reported using the synthetic peptide YSDSPSTST as the acceptor substrate [19].
• Deletion of mouse embryo fibroblast N-acetylglucosaminyltransferase V stimulates alpha5beta1 integrin expression mediated by the protein kinase C signaling pathway [20].

Regulatory relationships of Gcnt2

• The her-2/neu oncogene stimulates the transcription of N-acetylglucosaminyltransferase V and expression of its cell surface oligosaccharide products [21].

Other interactions of Gcnt2

• UDP-GlcNAc:Manalpha1-6Manbeta-R beta1-6-N-acetylglucosaminyltransferase V (GlcNAc-TV) and UDP-GlcNAc:Galbeta1-3GalNAc-R beta1-6-N-acetylglucosaminyltransferase (core 2 GlcNAc-T) are Golgi enzymes that catalyse the biosynthesis of beta1-6GlcNAc-branched intermediates in the N- and O-linked biosynthesis pathways, respectively [22].
• A key transferase in the generation of mature N-linked carbohydrates is the medial Golgi enzyme N-acetylglucosaminyltransferase I (EC 2.4.1.101; GlcNAc-TI) which is encoded by the Mgat-1 gene [23].
• The expression of Muc5ac messenger RNA (mRNA) as well as glycoprotein was enhanced on Day 2, peaked on Day 4, and decreased on Day 7, whereas enhanced expression of mucin core 2 beta6 N-acetylglucosaminyltransferase (C2GnT)-M mRNA was not detected until Day 4 and peaked on Day 7 [24].
• N-Acetylglucosaminyltransferase activity was elevated in 5.51 att- cells and likely responsible for the increased expression of GalTase oligosaccharide substrates [25].
• CL 3 cells have been shown to exhibit increased CMP-sialic acid:glycoprotein sialyltransferase and GM3 synthetase activities, whereas CL 6 cells have been shown to contain decreased UDPgalactose:glycoprotein galactosyltransferase and UDP-N-acetylglucosamine:glycoprotein N-acetylglucosaminyltransferase activities [26].

Analytical, diagnostic and therapeutic context of Gcnt2

• IGnT protein was detected by immunohistochemistry using the IGnT fusion-protein antibody [1].
• Northern blot analysis of beta-1, 4-GalTs I, II, III, IV, V, and VI and N-acetylglucosaminyltransferase (GlcNAcT)V in human cancer cell lines showed that the gene expression levels of beta-1,4-GalT V but not other beta-1,4-GalTs are strongly correlated with those of GlcNAcT V whose activity was shown to increase by malignant transformation [27].
• Changes in the enzymatic activities of other glycosyltransferases, such as alpha1,3-galactosyltransferase, and alpha-6-D-mannoside beta-1,6 N-acetylglucosaminyltransferase V, did not point to any interaction between GnT-III and these enzymes in the transgenic mice, suggesting that this approach may be useful in clinical xenotransplantation [28].

References