Expression cloning of a CMP-NeuAc:NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer alpha 2,8-sialyltransferase (GD3 synthase) from human melanoma cells.

Nara, Kiyomitsu; Watanabe, Yumiko; Maruyama, Kazuo; Kasahara, Kohji; Nagai, Yoshitaka; Sanai, Yutaka

doi:10.1073/pnas.91.17.7952

Cited by 111 publications

(47 citation statements)

References 50 publications

(39 reference statements)

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“…However, it has not been determined if ST8Sia IV or ST8Sia II can add polysialic acid more efficiently on a preformed disialyl structure, NeuNAc␣238NeuNAc␣233Gal-␤134GlcNAc3 R. In addition to ST8Sia IV and ST8Sia II, three more ␣2,8-sialyltransferases have been molecularly cloned. Among them, ST8Sia III (24) is more closely related to ST8Sia IV or ST8Sia II than to ST8Sia I (GD3/GT3 synthase) (25)(26)(27)(28) or ST8Sia V (GT3 synthase) (29). These studies also demonstrated that ST8Sia I and ST8Sia V utilize glycolipids as acceptors, whereas ST8Sia III forms disialic and oligosialic acid in both glycoproteins and glycolipids.…”

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confidence: 50%

Differential Biosynthesis of Polysialic Acid on Neural Cell Adhesion Molecule (NCAM) and Oligosaccharide Acceptors by Three Distinct α2,8-Sialyltransferases, ST8Sia IV (PST), ST8Sia II (STX), and ST8Sia III

Angata¹,

Suzuki²,

McAuliffe

et al. 2000

Journal of Biological Chemistry

103

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Polysialylated neural cell adhesion molecule (NCAM)is thought to play a critical role in neural development. Polysialylation of NCAM was shown to be achieved by two ␣2,8-polysialyltransferases, ST8Sia IV (PST) and ST8Sia II (STX), which are moderately related to another ␣2,8-sialyltransferase, ST8Sia III. Here we describe that all three ␣2,8-sialyltransferases can utilize oligosaccharides as acceptors but differ in the efficiency of adding polysialic acid on NCAM. First, we found that ST8Sia III can form polysialic acid on the enzyme itself (autopolysialylation) but not on NCAM. These discoveries prompted us to determine if ST8Sia IV and ST8Sia II share the property of ST8Sia III in utilizing low molecular weight oligosaccharides as acceptors. By using a newly established method, we found that ST8Sia IV, ST8Sia II, and ST8Sia III all add oligosialic and polysialic acid on various sialylated N-acetyllactosaminyl oligosaccharides, including NCAM N-glycans, fetuin N-glycans, synthetic sialylated N-acetyllactosamines, and on ␣ 2 -HS-glycoprotein. Our results also showed that monosialyl and disialyl N-acetyllactosamines can serve equally as an acceptor, suggesting that no initial addition of ␣2,8-sialic acid is necessary for the action of polysialyltransferases. Polysialylation of NCAM by ST8Sia IV and ST8Sia II is much more efficient than polysialylation of N-glycans isolated from NCAM. Moreover, ST8Sia IV and ST8Sia II catalyze polysialylation of NCAM much more efficiently than ST8Sia III. These results suggest that no specific acceptor recognition is involved in polysialylation of low molecular weight sialylated oligosaccharides, whereas the enzymes exhibit pronounced acceptor specificities if glycoproteins are used as acceptors.

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confidence: 50%

Differential Biosynthesis of Polysialic Acid on Neural Cell Adhesion Molecule (NCAM) and Oligosaccharide Acceptors by Three Distinct α2,8-Sialyltransferases, ST8Sia IV (PST), ST8Sia II (STX), and ST8Sia III

Angata¹,

Suzuki²,

McAuliffe

et al. 2000

Journal of Biological Chemistry

103

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“…The nearly total absence of disialogangliosides in highly metastatic cells is also a striking feature and we are currently investigating the relevance of GD3 synthase in the onset of the metastatic spread of T 1 C3 cells. The recent cloning of GD3 synthase from melanoma cells by Nara et al [36] shall offer valuable tools for such studies.…”

Section: Resultsmentioning

confidence: 99%

Deficiency of ganglioside biosynthesis in metastatic human melanoma cells: relevance of CMP‐NeuAc: LacCer α2‐3 sialyltransferase (GM3 synthase)

et al. 1995

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The glycosphingolipid patterns were analyzed on two clones derived from a human melanoma cell line and selected for their respectively high and low metastatic ability in immunosuppressed newborn rats. Conversely to the weakly metastatic cells which exhibited a pattern similar to that of the parental cell line, highly metastatic human melanoma cells appeared to be deficient in ganglioside biosynthesis. An accumulation of lactosylceramide was found in the latter cells, with low amounts of GM3 as the only ganglioside detected and a fourfold decreased activity of GM3 synthase (EC 2.4.99.9). After subcutaneous injection of metastatic cells in newborn rats, the cells proliferating in the tumor induced at the injection site re-expressed the four common gangliosides of melanoma: GM3, GM2, GD3 and GD2, whereas the cells growing in the lungs as metastatic nodules were deficient in ganglioside synthesis and showed an accumulation of lactosylceramide. Taken together, our results suggest that the human melanoma cells which are able to escape from the primary tumor and invade the lungs have an impaired ganglioside biosynthesis with a deficient GM3 synthase.

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“…Furthermore, sucrose density gradient analysis showed that Lyn, in both cerebella and CHO cells transfected with Lyn cDNA, was detected in the lipid raft fraction. R24 immunoprecipitated caveolin, a caveolae marker protein, from CHO cells transfected with GD3 synthase cDNA (22). These observations suggest that GSL may regulate the functions of Lyn in lipid rafts.…”

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confidence: 93%

Involvement of Gangliosides in Glycosylphosphatidylinositol-anchored Neuronal Cell Adhesion Molecule TAG-1 Signaling in Lipid Rafts

Kasahara¹,

Watanabe²,

Takeuchi³

et al. 2000

Journal of Biological Chemistry

144

129

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The association of ganglioside GD3 with TAG-1, a glycosylphosphatidylinositol-anchored neuronal cell adhesion molecule, was examined by coimmunoprecipitation experiments. Previously, we have shown that the anti-ganglioside GD3 antibody (R24) immunoprecipitated the Src family kinase Lyn from the rat cerebellum, and R24 treatment of primary cerebellar cultures induced Lyn activation and rapid tyrosine phosphorylation of an 80-kDa protein (p80). We now report that R24 coimmunoprecipitates a 135-kDa protein (p135) from primary cerebellar cultures. Treatment with phosphatidylinositol-specific phospholipase C revealed that p135 was glycosylphosphatidylinositol-anchored to the membrane. It was identified as TAG-1 by sequential immunoprecipitation with an anti-TAG-1 antibody. Antibody-mediated cross-linking of TAG-1 induced Lyn activation and rapid tyrosine phosphorylation of p80. Selective inhibitor for Src family kinases reduced the tyrosine phosphorylation of p80. Sucrose density gradient analysis revealed that the TAG-1 and tyrosine-phosphorylated p80 in cerebellar cultures were present in the lipid raft fraction. These data show that TAG-1 transduces signals via Lyn to p80 in the lipid rafts of the cerebellum. Furthermore, degradation of cell-surface glycosphingolipids by endoglycoceramidase induced an alteration of TAG-1 distribution on an OptiPrep gradient and reduced the TAG-1-mediated Lyn activation and tyrosine phosphorylation of p80. These observations suggest that glycosphingolipids are involved in TAG-1-mediated signaling in lipid rafts.Gangliosides, sialic acid-containing glycosphingolipids (GSLs), 1 are found in the outer leaflet of the plasma membrane of all vertebrate cells and are thought to play functional roles in cellular interactions and the control of cell proliferation (1-4).In the nervous system, where gangliosides are particularly abundant, the species and amounts of gangliosides undergo profound changes during development, suggesting that they may play fundamental roles in this process (5). The accumulation of gangliosides within the neurons in ganglioside storage diseases results in extensive neurite outgrowth (6). Exogenously administered gangliosides accelerate the regeneration of neurons in the central nervous system in vivo after lesioning (7). The addition of exogenous gangliosides to primary cultures of neurons and neuroblastoma cells in vitro stimulates cellular differentiation with concomitant neurite sprouting and extension (8 -10). Glucosylceramide synthesis, the first glycosylation step of GSL synthesis, is required for axonal growth in hippocampal neurons (11) and for embryonic development (12). Transfection of the ganglioside GD3 2 synthase cDNA into neuroblastoma cells induces their cholinergic differentiation and neurite sprouting (13). Finally, mice lacking complex gangliosides exhibit axonal degeneration (14). These data show that gangliosides are involved in neural cell differentiation and brain development. However, the molecular mechanisms underlying the ganglioside-depend...

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Expression cloning of a CMP-NeuAc:NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer alpha 2,8-sialyltransferase (GD3 synthase) from human melanoma cells.

Cited by 111 publications

References 50 publications

Differential Biosynthesis of Polysialic Acid on Neural Cell Adhesion Molecule (NCAM) and Oligosaccharide Acceptors by Three Distinct α2,8-Sialyltransferases, ST8Sia IV (PST), ST8Sia II (STX), and ST8Sia III

Differential Biosynthesis of Polysialic Acid on Neural Cell Adhesion Molecule (NCAM) and Oligosaccharide Acceptors by Three Distinct α2,8-Sialyltransferases, ST8Sia IV (PST), ST8Sia II (STX), and ST8Sia III

Deficiency of ganglioside biosynthesis in metastatic human melanoma cells: relevance of CMP‐NeuAc: LacCer α2‐3 sialyltransferase (GM3 synthase)

Involvement of Gangliosides in Glycosylphosphatidylinositol-anchored Neuronal Cell Adhesion Molecule TAG-1 Signaling in Lipid Rafts

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