Some 14β-cyanoandrostane derivatives

Campbell, Alex C.; Lawrie, W.; McLean, John H.

doi:10.1039/j39690000554

Cited by 9 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the Chinese-hamster-ovary mutant cell lines LEC 11 and LEC 12, two distinct fucosyltransferase activities have been described [15]. The enzyme from LEC 11 cells resembles the plasma type enzyme, catalyzing transfer of fucose to sialylated substrates, and, in the case of polylactosamine sequences, it has a preference for transferring fucose to internal GlcNAc residues [29].…”

Section: Discussionmentioning

confidence: 99%

The use of human milk fucosyltransferase in the synthesis of tumor‐associated trimeric X determinants

Vries

Norberg

Lönn

et al. 1993

European Journal of Biochemistry

View full text Add to dashboard Cite

We have studied the fucosylation of a chemically synthesized trimer of N-acetyllactosamine [(LacNAc),-EtPhNHCOCF,] with a fucosyltransferase preparation from normal human milk, which utilizes both type-1 and type-2 structures, whether sialylated or not. When fucose residues were added enzymically to the (LacNAc),-EtPhNHCOCF, hexasaccharide, mono-, di-, or trifucosylated oligosaccharide species were formed, containing the LewisX determinant (Gal~l+4[Fucal+3]GlcNAcPl-3). With excess GDP-fucose and prolonged reaction times, the trifucosylated product was formed in almost quantitative yield. Kinetic analysis of the fucosylation reaction indicated that there is a significant difference in the rate of transfer of the first, second and third fucose residues onto the acceptor molecule. The location of the fucose residues in the monofucosylated and difucosylated intermediate products was assessed by analyzing the digests obtained after endo-P-galactosidase treatment by HPLC and reverse-phase chromatography. In addition, the fucosylated (LacNAc),-EtPhNHCOCF, structures were characterized by HPLC and were identified by 400-MHz 'H-NMR spectroscopy. There is a highly preferred order in which the fucosyl residues are attached to (LacNAc),-EtPhNHCOCF,. In the major pathway, the first two fucose residues are transferred with equal preference to the medial (GN3) and proximal (GN1) GlcNAc residues, whereas the third fucose is attached to the distal (GN5) GlcNAc residue. These results are of relevance in understanding the role of a-3-fucosyltransferase in the biosynthesis of LewisX-related cell-surface carbohydrate structures, that function as ligands for selectin-type cell-adhesion molecules and may play a role in the invasion and metastasis of several carcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

The use of human milk fucosyltransferase in the synthesis of tumor‐associated trimeric X determinants

Vries

Norberg

Lönn

et al. 1993

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…Unlike receptor tyrosine kinases, receptors of this family do not have kinase domains and show only limited similarity in their cytoplasmic regions consisting in box 1 and box 2 motifs [3]. Binding of GH induces dimerisation of its receptor [4], activation of the GHR associated kinase Jak 2 [5], and initiation of a cascade of protein tyrosine phosphorylations [6]. Jak 2 is also involved in the signaling pathway of several receptors of the family (review in [7]).…”

Section: Introductionmentioning

confidence: 99%

The membrane proximal region of the cytoplasmic domain of the growth hormone receptor is involved in the activation of Stat 3

et al. 1995

View full text Add to dashboard Cite

Growth hormone receptor (GHR) signaling involves activation of the Janus Kinases (Jak) and of Stat proteins (signal transducers and activators of transcription). Growth hormone (GH) induces transcriptional activation of c-los gene and the c-sis inducible element (SIE) of its promoter was shown to bind the Stat proteins. Using cells co-transfected with GHR and Stat 3 expression vectors, we directly demonstrate that GH induces tyrosine phosphorylation of Stat 3 and its binding to the SIE probe. We showed, using mutant forms of GHR, that only the cytoplasmic membrane proximal domain of the receptor, including a conserved proline rich region (box 1), is required for this effect.

show abstract

“…Prieels et al have presented evidence using oligosaccharide substrates that a1 +3 and a1 +4 fucosyl transferase activities from human milk co-purify [ll]. Campbell and Stanley have described two, a1 -3 fucosyl transferase activities in Chinese hamster mutants which differ in glycoprotein acceptor specificity [12]. Hakomori has presented an interesting hypothesis which predicts that 'aberrant' fucosylation of Lea to Leb may occur in relation to oncogenesis [13].…”

mentioning

confidence: 99%

Biosynthesis of Lewis fucolipid antigens in human colorectal carcinoma cells. Partial characterization of LcOse4Cer and H-1 fucolipid fucosyl transferase acceptor activities

Liepkans

Larson

1987

Eur J Biochem

View full text Add to dashboard Cite

Purified glycolipids were tested for their ability to serve as acceptors of ['4C]fucose from GDP-['4C]fucose as catalyzed by cell-free extracts and purified membrane fractions of human colorectal carcinoma cells, SW1116, cultured in serum-free medium. Purified lactotetraosyl ceramide (GalP1+3GlcNAcPl+ 3GalP1+4Glc-Cer or LcOse4Cer) and H-1 glycolipid (Fucal+2Gal~1+3GlcNAc~1+3Gal~1+4Glc-Cer or IV2 FucaLcOse4Cer) stimulated incorporation of radioactivity into lipid-soluble glycolipid at a rate greater than ten times that of Lea glycolipid [Gal~1+3(Fucal+4)GlcNAc~1+3Gal~1+4Glc-Cer or 1114 FucaLcOse4Cer].The enzymatic activities in crude and purified membrane fractions were optimized for substrate concentrations (glycolipid and GDP-fucose), detergent requirement (taurocholate), pH, time and protein. The radioactive product of H-1 fucosylation migrated as discrete and distinct bands on high-performance thin-layer chromatograms (HPTLC). Evidence for their identity with Leb fucolipid described previouslyThe radioactive product of LcOse4Cer fucosylation was mainly Lea fucolipid as determined by co-migration with authentic Lea fucolipid in three HPTLC systems as native and acetylated derivatives. Our results also indicated a low level of H-1 and Leb glycolipid synthesis from LcOse4Cer.On the basis of the optima, linearity for time, and enzyme-limiting conditions, we obtained a 12-19-fold purification of the LcOse4Cer and H-1 fucosyl transferase acceptor activities in three peaks of a sucrose gradient. The peak with the highest specific activity (peak 3) was highest in density and in Na', K', ATPase specific activity, although NADH -cytochrome-c reductase and UDP-GalNac transferase were also present in peak 3.The apparent K , values of LcOse4Cer acceptor activity and H-1 acceptor activity in peak 3 were significantly different 0) < 0.01) by statistical tests, 2.4 pM and 0.5 pM, respectively. These apparent K , values were much lower (lo3 x ) and the pH optima were lower (4.8 -5.3), than the corresponding properties reported for the a1 +3/ a1 4 4 fucosyl transferase purified from human milk. Our results suggest a role for the non-glycosidic moieties of the acceptors and/or the tissue-specific or primitive expression of these fucosyl transferase activities.

show abstract

Some 14β-cyanoandrostane derivatives

Cited by 9 publications

References 0 publications

The use of human milk fucosyltransferase in the synthesis of tumor‐associated trimeric X determinants

The use of human milk fucosyltransferase in the synthesis of tumor‐associated trimeric X determinants

The membrane proximal region of the cytoplasmic domain of the growth hormone receptor is involved in the activation of Stat 3

Biosynthesis of Lewis fucolipid antigens in human colorectal carcinoma cells. Partial characterization of LcOse4Cer and H-1 fucolipid fucosyl transferase acceptor activities

Contact Info

Product

Resources

About