Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.99.6 (sialyltransferase)
 1,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rat brain Golgi sialyltransferase activity capable of the differentiation-dependent control of N-CAM sialylation state is described. The specific activity of Golgi sialyltransferase was found to be developmentally regulated with respect to both endogenous and exogenous protein acceptors, with a particular elevation on postnatal days 10-12 when the heavily sialylated or 'embryonic' form of N-CAM is re-expressed. The subsequent developmental decrease in activity was associated with a significant decrease in apparent Km for the CMP-NeuNAc substrate, but not for the asialofetuin exogenous acceptor, which could not be attributed to the temporal expression of an endogenous competitive inhibitor. The apparent Vmax remained constant for CMP-NeuNAc but was significantly reduced for asialofetuin. Sialyltransferase activity, which was optimal at pH 7.0-7.5, was also modulated by various cations. Zinc abolished enzyme function, in contrast to ferric ions which stimulated activity fourfold-sevenfold. The marked activation of the adult form of the enzyme by potassium and magnesium ions, together with the alterations in kinetic constants, suggested this activity to be distinct from that derived from postnatal day-12 tissue. The kinetics of [14C]sialic acid incorporation into immuno-precipitated N-CAM demonstrated the individual polypeptides to be sialylated, possibly by addition of polysialosyl units, in a developmental sequence. The presence of four distinct sialyltransferase activities was demonstrated by non-denaturing gel electrophoresis followed by solid-phase enzyme assay. These isoforms were temporally expressed during development, two being correlated with the postnatal reexpression of the 'embryonic' form of N-CAM.
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PMID:Developmental control of N-CAM sialylation state by Golgi sialyltransferase isoforms. 325 55

The neural cell adhesion molecule N-CAM is believed to be intimately involved in the structuring of the central nervous system. During post-natal development the molecule exists in 2 forms--a sialic acid-rich form which is preferentially expressed during cell acquisition and fibre outgrowth and a sialic acid-poor form which appears at times coincident with synaptogenesis. The developmental changes between these 2 forms have been demonstrated to be impaired by chronic low-level lead exposure and this is consistent with the reduced synaptic elaboration associated with this action. Here is described the effect of lead on the Golgi-associated sialyltransferase which regulates N-CAM sialylation state. Lead chloride was found to markedly stimulate sialyltransferase with an ED50 of 5 X 10(-7) M in adult Golgi fractions. This was not observed in fractions derived from 12-day old animals. At the concentration of 5 X 10(-5) M lead was found to have a differential effect on the developmental expression of this enzyme. During the early phases of development (days 4-16) sialyltransferase activity was inhibited. However, in coincidence with periods of N-CAM desialylation (days 16-30), it was significantly stimulated. These findings are related to the perturbations of N-CAM function during chronic low-level lead exposure.
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PMID:Lead stimulates Golgi sialyltransferase at times coincident with the embryonic to adult conversion of the neural cell adhesion molecule (N-CAM). 337 25

Golgi-enriched fractions have been isolated from rat brain of increasing postnatal age and defined by electron microscopy and distribution of marker enzymes. The expression of sialyltransferase activity associated with these fractions has been demonstrated to developmentally decrease and this appeared to be, in part, dependent on endogenous competitive inhibition. The developmental regulation of this activity paralleled the sialylation state of the neural cell adhesion molecule (D2-CAM/N-CAM) and could be demonstrated to be capable of endogenously sialylating this protein in the isolated Golgi fractions. In 12-day-old animals the majority of the transferred [14C]sialic acid was found to be associated with the high-molecular-weight [greater than 200 kilodaltons (kd)] form of D2-CAM/N-CAM, indicative of the protein having been heavily sialylated. Sialylation of the individual D2-CAM/N-CAM polypeptides was also demonstrated in both 12-day and adult animals and transfer was evident only in the 180-kd and 115-kd components and not in the 140-kd component. In contrast, Golgi-enriched fractions prepared from adult animals showed little capability of heavily sialylating D2-CAM/N-CAM to any significant extent.
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PMID:Postnatal D2-CAM/N-CAM sialylation state is controlled by a developmentally regulated Golgi sialyltransferase. 355 63

Polysialic acid, or PSA, is a term used to refer to linear homopolymers of alpha(2,8)-sialic acid residues displayed at the surface of some mammalian cells. PSA is typically linked to the neural cell adhesion molecule N-CAM, where it can modulate the homotypic adhesive properties of this polypeptide. PSA expression is developmentally regulated, presumably through mechanisms involving regulated expression of sialyltransferases involved in PSA biosynthesis. Several different sialytransferase sequences have been implicated in PSA expression, although the precise roles of these enzymes in this context remain unclear. One such sequence, termed STX, maintains approximately 59% amino acid sequence identity with another sialyltransferase (PST-1, from hamster; PST, human) that is known to participate in PSA expression. While a murine STX fusion protein can catalyze the synthesis of a single alpha(2,8)-sialic acid linkage in vitro, the ability of STX to participate in PSA expression in vivo has not been demonstrated. We show here that STX transcripts are present in a PSA-positive, N-CAM-positive human small cell carcinoma line (NCI-H69/F3), but are absent in a variant of this line (NCI-H69/E2) selected to be PSA-negative and N-CAM-positive. To functionally confirm this correlation, we have cloned a human cDNA encoding the human STX sequence, and show, by transfection studies, that human STX can restore PSA expression when expressed in the PSA-negative, N-CAM-positive small cell carcinoma variant. We furthermore show that STX can confer PSA expression when expressed in a PSA-negative, N-CAM-positive murine cell line (NIH-3T3 cells), or when expressed in PSA-negative, N-CAM-negative COS-7 cells. These observations imply that STX, like PST-1/PST, can determine PSA expression in vivo. When considered together with the correlation between STX expression and PSA expression in vivo in the brain, these results suggest a regulatory role for STX in PSA expression in the developing central nervous system and small cell lung carcinoma.
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PMID:A human STX cDNA confers polysialic acid expression in mammalian cells. 755 89

We have detected sialyltransferase activity of recombinant mouse STX, which was cloned from rat brain as a new member of the sialyltransferase family, but sialyltransferase activity of which had not been detected previously [Livingston and Paulson, J. Biol. Chem. (1993) 268, 11504-11507]. The activity of mouse STX was specific toward sialylated glycoproteins. N-Glycanase treatment and linkage-specific sialidase treatment of glycoproteins revealed that STX transfers sialic acids through alpha 2,8-linkages to only N-linked oligosaccharides of glycoproteins. However, polymerase activity for polysialic acid synthesis was not detected for this sialyltransferase. Since this alpha 2,8-sialyltransferase gene is highly restricted in fetal and newborn brain, it may be involved in the polysialylation of glycoproteins, especially of N-CAM.
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PMID:Enzymatic activity of a developmentally regulated member of the sialyltransferase family (STX): evidence for alpha 2,8-sialyltransferase activity toward N-linked oligosaccharides. 787 91

The function of the neural cell adhesion molecule, NCAM, is modulated by the expression of the N-linked polysialic acid (PSA) oligosaccharide chain, with PSA serving to decrease the adhesive potential of the protein backbone. In this study, we have generated clonal cells of the rat B104 and human SH-SY5Y neuroblastoma cell lines that over-express the alpha2,6(N) sialyltransferase (ST6N) enzyme in order to investigate the role of this enzyme in PSA biosynthesis. The clonal cells exhibited ST enzyme activities of up to 20-times control levels, which remained stable throughout the duration of the study. The increase in enzyme activity paralleled an increase in enzyme protein levels, as determined by Western blot analysis, and immunocytochemical analysis confirmed the Golgi localisation of the enzyme. The induction of PSA-NCAM expression in the cells expressing high levels of ST6N was confirmed both by using anti-PSA antisera and by specific digestion with endo-N-acetylneuraminidase E, whose actions are specific for alpha2, 8-linked PSA chains. These results demonstrate that the cellular ST6N activity serves to positively influence the expression of PSA in neuronal cells.
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PMID:Overexpression of the alpha2,6 (N) sialyltransferase enzyme in human and rat neural cell lines is associated with increased expression of the polysialic acid epitope. 1056 92

Sialoglycoproteins play a key role in both brain development and neuronal plasticity with their sialylation state being controlled by the sialyltransferase (STN) family of enzymes. In this study, we have determined the role of specific kinase enzymes in the expression and catalytic activity of the alpha2,6 STN (ST6N) isozyme. The catalytic activity was moderately decreased following the inhibition of GSK3beta with LiCl. However, there was a significant increase in catalytic activity following activation of protein kinase C (PKC) by phorbol ester. There was no change in the expression levels of the enzyme protein following any of the treatments. The changes in enzyme catalytic activity were also mirrored by the expression of both protein-bound sialic acid and the polysialic acid oligosaccharide group attached to the neural cell adhesion molecule, NCAM. These results provide further evidence for the role of second messenger-associated kinase enzymes in the modulation of the cell glycosylation potential.
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PMID:The role of protein phosphorylation in alpha2,6(N)-sialyltransferase activity. 1294 59

Estrogen-induced synaptic plasticity (EISP) in the periventricular area (PVA) of the hypothalamus is necessary for the preovulatory gonadotropin surge. Because in situ enzymatic desialization of hypothalamic polysialylated (PSA) neural cell adhesion molecule (NCAM) blocked EISP, we examined the presence and amount of NCAM isotopes, PSA-NCAM, and sialylation enzymes in microdissected mouse hypothalamus tissues from proestrous afternoon [peak of estrogens and nadir of arcuate nucleus (AN) synapses] and metestrous morning (nadir of estrogens and highest AN synapses). Immunohistochemistry confirmed immunoreactive (ir) PSA-NCAM staining in the perineural spaces of the PVA. The extent of staining was cycle dependent, with more dense and complete profiles of individual neurons limned by the ir-PSA-NCAM staining on proestrus and less on metestrus. Western blots showed that high levels of ir-PSA-NCAM on proestrus are accompanied by diminished ir-NCAM-140 and -180 but not ir-NCAM-120 and the reverse on metestrus (P < 0.05). To evaluate the increase of sialylated NCAM at the expense of desialylated protein, expression of the responsible polysialyltransferase enzymes polysialyltransferase (ST8Sia IV) and sialyltransferase (ST8Sia II) mRNA levels were measured using RT-PCR. Both polysialyltransferase and sialyltransferase mRNA are more abundant on proestrus than metestrus (P < 0.05), indicating that these enzymes are regulated by estrogens. These results support estrogen-regulated formation and extrusion of hydrophilic PSA-NCAM into perineural spaces in the PVA as part of the mechanism of EISP.
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PMID:Estrogens regulate posttranslational modification of neural cell adhesion molecule during the estrogen-induced gonadotropin surge. 1928 89