Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q7LGC8 (HSD)
 3,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between cAMP and protein kinase C in the regulation of 3 beta-hydroxysteroid dehydrogenase (3 beta HSD), 17 alpha-hydroxylase, and sulfotransferase was examined in human fetal adrenocortical cells under defined serum-free conditions in culture. Forskolin induced 3 beta HSD and 17 alpha-hydroxylase in a dose-dependent manner, with maximal effects at 10 microM. 12-O-Tetradecanoyl phorbol 13-acetate (TPA) at 1 nM depressed the induction of 17 alpha-hydroxylase activity by forskolin by more than 95% and increased the stimulation of 3 beta HSD activity by forskolin by 4- to 5-fold. Increases were maximal at 48-72 h of incubation. Dehydroepiandrosterone sulfotransferase activity increased over 48 h when cells were transferred to serum-free defined medium. Addition of 10 microM forskolin stimulated sulfotransferase activity only when cells remained in 10% serum. TPA at 1 nM inhibited the increase in sulfotransferase activity. The concentration of TPA required for inhibition of forskolin-stimulated 17 alpha-hydroxylase and sulfotransferase activity was similar to that required for enhancement of forskolin-induced 3 beta HSD activity, suggesting that comparable levels of C kinase activation are involved in these events. Angiotensin II, carbachol, epidermal growth factor, and fibroblast growth factor had actions similar to those of TPA on one or more of these enzyme activities. TPA also had similar actions on enzyme activities when they were stimulated by cAMP analogs rather than by forskolin. These studies suggest that adrenal steroid biosynthesis is under dual regulation by cAMP and protein kinase C. cAMP induces enzymes required for synthesis of 17 alpha-hydroxylated steroids, including the adrenal androgens. Activation of protein kinase C may play a complementary role by enhancing the induction of enzymes required for non-17 alpha-hydroxylated steroid biosynthesis and inhibiting those involved in the synthesis of androgens.
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PMID:Dual regulation of 3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase, and dehydroepiandrosterone sulfotransferase by adenosine 3',5'-monophosphate and activators of protein kinase C in cultured human adrenocortical cells. 283 83

A soluble sulfotransferase that could 6-sulfate both chondroitin sulfate and corneal keratan sulfate was purified 27,500-fold using a sequence of affinity chromatographic steps with heparin-Sepharose, wheat germ agglutinin-agarose, and 3',5'-ADP-agarose. The essentially pure enzyme had a specific activity 40 times greater than the most purified chondroitin 6-sulfotransferase previously reported and exhibited a single sharp Coomassie Blue-stained and a heavy silver-stained protein band of 75 kDa on SDS-polyacrylamide gel electrophoresis. Chromatography of the purified enzyme on Sephacryl demonstrated a size of 150 kDa, which indicated that the native enzyme exists as a dimer. In addition to 6-sulfation of nonsulfated GalNAc, the purified serum enzyme had the ability to sulfate GalNAc 4-sulfate residues to give GalNAc 4,6-disulfate residues. The purified enzyme exhibited a Km of 40 microM for adenosine 3'-phosphate 5'-phosphosulfate when either chondroitin sulfate or corneal keratan sulfate were used as the acceptors. Use of both chondroitin sulfate and keratan sulfate in the same experiment demonstrated mutual competition, establishing that the sulfation of these substrates is by the same enzyme. Photoaffinity labeling of the purified enzyme with 2-azidoadenosine 3',5'-di[5'-32P]phosphate occurred only with the 75-kDa protein, confirming that this is the chondroitin 6-sulfotransferase/keratan sulfotransferase.
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PMID:Purification, photoaffinity labeling, and characterization of a single enzyme for 6-sulfation of both chondroitin sulfate and keratan sulfate. 767 38

Chondroitin 6-sulfotransferase, which transfers sulfate from 3'-phosphoadenylyl sulfate to position 6 of N-acetylgalactosamine in chondroitin, was purified 1,430-fold to apparent homogeneity with a 22% yield from the serum-free culture medium of chick embryo chondrocytes by affinity chromatography on heparin-Sepharose CL-6B, wheat germ agglutinin-agarose, and 3',5'-ADP-agarose. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified enzyme showed a single broad protein band with an apparent molecular weight of 75,000. Since the purified enzyme has an apparent molecular weight of 160,000 as judged by gel chromatography on Superose 12, the active form of chondroitin 6-sulfotransferase may be a dimer. The purified enzyme transferred sulfate to chondroitin, chondroitin sulfate, and corneal keratan sulfate. Chondroitin sulfate E from squid cartilage, dermatan, sulfate, and heparan sulfate hardly served as acceptors of the sulfotransferase. The sulfated product derived from keratan sulfate was degraded by keratanase but not by chondroitinase ABC.
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PMID:Purification of chondroitin 6-sulfotransferase secreted from cultured chick embryo chondrocytes. 840 53

Developmentally regulated and cell type-specific expression of distinct sulfated glycosaminoglycan structures on cell surface proteoglycans is increasingly recognized as providing information relevant to cell-cell interactions and differentiation in developing organisms. In this report, developmental regulation of both the sulfation profile of chondroitin sulfate chains and activities of chondroitin 4-sulfotransferase (C4ST) and chondroitin 6-sulfotransferase (C6ST) were evaluated in embryonic chicken brain. The results revealed that the sulfation profile and the sulfotransferase activities changed markedly with development, and these alterations were precisely coordinated. Specifically, the proportions of both chondroitin 6-sulfate to 4-sulfate and C6ST to C4ST activities progressively decreased with development. In addition, the total amounts of both chondroitin sulfate chains and the sulfotransferase activities were highest during early embryonic stages and decreased sharply as the development reached completion. The developmental expression of the C6ST gene was also found to parallel the developmental down-regulation of both the C6ST activity and the chondroitin 6-sulfate structure. These findings suggest that the developmentally regulated expression of the sulfotransferases is a predominant factor for stage-specific regulation of chondroitin sulfate structures.
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PMID:Developmental regulation of the sulfation profile of chondroitin sulfate chains in the chicken embryo brain. 939 68

We have previously cloned chondroitin 6-sulfotransferase (C6ST) cDNA from chick embryo chondrocytes. C6ST catalyzes sulfation of chondroitin, keratan sulfate, and sialyl N-acetyllactosamine oligosaccharides. In this study, we report the cloning and characterization of a novel sulfotransferase that catalyzes sulfation of keratan sulfate. This new sulfotransferase cDNA clone was obtained from a human fetal brain library by cross-hybridization with chick C6ST cDNA. The cDNA clone obtained contains a single open reading frame that predicts a type II transmembrane protein composed of 411 amino acid residues. When the cDNA was introduced into a eukaryotic expression vector and transfected in COS-7 cells, keratan sulfate sulfotransferase activity was overexpressed, but C6ST activity was not increased over that of the control. Structural analysis of 35S-labeled glycosaminoglycan, which was formed from keratan sulfate by the reaction with 35S-labeled 3'-phosphoadenosine 5'-phosphosulfate and the recombinant sulfotransferase, showed that keratan sulfate was sulfated at position 6 of Gal residues. On the basis of the acceptor substrate specificity, we propose keratan sulfate Gal-6-sulfotransferase (KSGal6ST) for the name of the newly cloned sulfotransferase. KSGal6ST was assigned to chromosome 11p11. 1-11.2 by fluorescence in situ hybridization. Among various human adult tissues, a 2.8-kilobase message of KSGal6ST was expressed mainly in the brain. When poly(A)+ RNAs from the chick embryo cornea and brain were probed with the human KSGal6ST cDNA in Northern hybridization, a clear band with about 2.8 kilobases was detected. These observations suggest that KSGal6ST may participate in the biosynthesis of keratan sulfate in the brain and cornea.
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PMID:Molecular cloning and characterization of human keratan sulfate Gal-6-sulfotransferase. 940 39

Chondroitin 6-sulfotransferase (C6ST) catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to position 6 of the N-acetylgalactosamine residue of chondroitin. Using chick C6ST cDNA as a probe, we cloned the cDNA of mouse C6ST. The mouse enzyme was predicted to be composed of 472 amino acids, and exhibited 71% sequence identity with the chicken enzyme. The mouse and chicken catalytic domains exposed to the luminal side exhibited 81% identity, while the homology of the remaining regions was less. Transfection and expression of the mouse cDNA in COS-7 cells yielded C6ST activity. Keratan sulfate sulfotransferase activity, which was simultaneously expressed, amounted to 3% of the C6ST activity, this value being significantly lower than that observed in the case of the chicken enzyme. Mouse C6ST mRNA was strongly expressed in the spleen, lung, and eye. In situ hybridization revealed that the transcript was localized in stromal cells in the marginal zone and red pulp of the spleen, and stromal cells in the bone marrow. Fluorescence in situ hybridization analysis revealed the gene is located in mouse chromosome 9.
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PMID:Mouse chondroitin 6-sulfotransferase: molecular cloning, characterization and chromosomal mapping. 959 47

We isolated a cDNA clone encoding mouse N-acetylglucosamine-6-O-sulfotransferase based on sequence homology to the previously cloned mouse chondroitin 6-sulfotransferase. The cDNA clone contained an open reading frame that predicts a type II transmembrane protein composed of 483 amino acid residues. The expressed enzyme transferred sulfate to the 6 position of nonreducing GlcNAc in GlcNAcbeta1-3Galbeta1-4GlcNAc. Galbeta1-4GlcNAcbeta1-3Galbeta1-4GlcNAc and various glycosaminoglycans did not serve as acceptors. Expression of the cDNA in COS-7 cells resulted in production of a cell-surface antigen, the epitope of which was NeuAcalpha2-3Galbeta1-4(SO4-6)GlcNAc; double transfection with fucosyltransferase IV yielded Galbeta1-4(Fucalpha1-3)(SO4-6)GlcNAc antigen. The sulfotransferase mRNA was strongly expressed in the cerebrum, cerebellum, eye, pancreas, and lung of adult mice. In situ hybridization revealed that the mRNA was localized in high endothelial venules of mesenteric lymph nodes. The sulfotransferase was concluded to be involved in biosynthesis of glycoconjugates bearing the 6-sulfo N-acetyllactosamine structure such as 6-sulfo sialyl Lewis X. The products of the sulfotransferase probably include glycoconjugates with intercellular recognition signals; one candidate of such a glycoconjugate is an L-selectin ligand.
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PMID:Molecular cloning and characterization of an N-acetylglucosamine-6-O-sulfotransferase. 971 85

The cDNA and gene encoding human chondroitin 6-sulfotransferase (C6ST) have been cloned. The expression of a soluble recombinant form of the protein in COS-1 cells produced an active sulfotransferase, which used as acceptor substrates polymer chondroitin, various chondroitin sulfate isoforms and chondroitin sulfate tetrasaccharides. The identification of the reaction products demonstrated that the enzyme transferred sulfate to position 6 of GalNAc in the GlcAbeta1-3GalNAc but not the IdoAalpha1-3GalNAc nor the GlcAbeta1-3GalNAc(4-O-sulfate) sequences. The human C6ST gene spans more than 20 kb and consists of three exons. The protein-coding domain of the C6ST gene is divided into two discrete exons.
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PMID:Functional expression and genomic structure of human chondroitin 6-sulfotransferase. 988 91

Sulfation is essential for the generation of functional vascular endothelial cell ligands for the leukocyte adhesion molecule, L-selectin. Therefore, human vascular endothelium cDNA libraries were screened to identify sulfotransferases homologous to chicken chondroitin 6-sulfotransferase (C6ST). Two sulfotransferases were identified: CHST2, a novel 530-amino-acid sulfotransferase with a carboxyl-terminal region that was 45 and 43% homologous with those of human and chicken C6ST, respectively, and CHST1, which was identical to human C6ST. Northern blot analysis showed that CHST2 was broadly expressed among tissues. The CHST2 gene mapped to human chromosome 3q24 close to 3q25. Thus, this study identified two sulfotransferases expressed by vascular endothelial cells that may contribute to the generation of L-selectin ligands during inflammatory responses.
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PMID:CHST1 and CHST2 sulfotransferases expressed by human vascular endothelial cells: cDNA cloning, expression, and chromosomal localization. 1004 91

A novel human chondroitin 6-O-sulfotransferase, designated C6ST-2, was identified by BLAST analysis of expressed sequence tag using the sequence of a previously described human chondroitin 6-O-sulfotransferase (C6ST-1) as a probe. The new cDNA sequence revealed an open reading frame coding for a protein of 486 amino acids with a type II transmembrane protein topology. The amino acid sequence displayed 24% identity to the human C6ST-1, and the highest sequence identity was found in the COOH-terminal catalytic domain. The expression of a soluble recombinant form of the protein in COS-1 cells produced an active sulfotransferase with marked specificity for polymer chondroitin. In contrast, keratan sulfate and oligosaccharides containing the Galbeta1-4GlcNAc sequence, which are good acceptor substrates for the C6ST-1, hardly served as acceptors. The identification of the reaction product indicated that the enzyme is a novel chondroitin 6-O-sulfotransferase (C6ST-2) that mainly transfers sulfate to N-acetylgalactosamine. The coding region of C6ST-2 was contained in a single exon and localized to chromosome Xp11. Northern blot analysis of human brain poly(A)(+) RNA revealed a single transcript of 2.4 kilobase pairs. Reverse transcription-polymerase chain reaction analysis showed that C6ST-2 is developmentally regulated in various tissues with expression persisting through adulthood in the spleen. Thus, we demonstrated the redundancy in chondroitin 6-O-sulfotransferases capable of forming chondroitin 6-sulfate, which is important for understanding the mechanisms leading to specific changes in the sulfation profile of chondroitin sulfate chains in various tissues during development and malignant transformation.
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PMID:Molecular cloning and expression of a novel chondroitin 6-O-sulfotransferase. 1078 96


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