Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A motor neuron disorder resembling that of amyotrophic lateral sclerosis was found in a patient who had received the intramuscular administration of a mixture of bovine brain gangliosides (Yuki, N., Sato, S., Miyatake, T., Sugiyama, K., Katagiri, T., and Sasaki, H. (1991) Lancet 337, 1109-1110). A very high titer of anti-GM2 IgM was detected in the patient's serum and the patient quickly recovered after plasmapheresis. The clinical course of the patient appeared to be different from amyotrophic lateral sclerosis and the anti-GM2 IgM was thought to be the culprit. The IgM reacted with GM2, GM1b-GalNAc, SPG(alpha 2-3)-GalNAc, and GD1a-GalNAc, but not with GA2 or GD2, meaning that the epitope recognized by the IgM was the GM2-like terminal structure, GalNAc beta 1-4(Neu-Ac alpha 2-3)Gal beta 1-. In this study, we found two novel GM2-epitope containing gangliosides, X1 and X2, in bovine brain gangliosides by TLC immunostaining using the patient's IgM. They were characterized as unique lacto-ganglio type gangliosides containing the following branching structures. [formula: see text] Their unusual structures may be immunogenic to humans to induce anti-GM2 antibody.
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PMID:Novel lacto-ganglio type gangliosides with GM2-epitope in bovine brain which react with IgM from a patient of the amyotrophic lateral sclerosis-like disorder. 769 4

Alkaline borohydride-reduced keratan sulphate chains from bovine articular cartilage (6-8-year-old animals) were subjected to a limit digest with the enzyme keratanase II. Using 1H-NMR spectroscopy, 25 reduced oligosaccharides deriving from keratan sulphate were shown to have the following structures [GlcNAc(6S)-ol represents N-acetylglucosaminitol 6-O-sulphate]: Gal beta 1-4-GlcNAc(6S)-ol, Gal beta 1-4GlcNAc(6S)beta 1-3Gal beta 1-4GlcNAc(6S)-ol, Gal(6S)beta 1-4GlcNAc(6S)-ol, Gal-(6S)beta 1-4GlcNAc(6S) beta 1-3Gal beta 1-4GlcNAc(6S)-ol, Gal beta 1-4GlcNAc(6S)beta 1-3Gal(6S)beta 1-4GlcNAc(6S)-ol, Gal(6S)beta 1-4GlcNAc(6S)beta 1-3Gal(6S)1-4GlcNAc(6S)-ol, Gal beta 1-4(Fuc alpha 1-3)GlcNAc(6S)-ol, Gal beta 1-4-(Fuc alpha 1-3)GlcNAc(6S)beta1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc(6S)-ol, Gal beta 1-4GlcNAc(6S)beta 1-3Gal beta 1-4(Fuc alpha 1-3)-GlcNAc(6S)-ol, Gal beta 1-4(Fuc alpha 1-3)GlcNAc(6S)beta 1-3Gal beta 1-4GlcNAc(6S)-ol, Gal(6S) beta 1-4GlcNAc-(6S)beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc(6S)-ol, Gal beta 1-4(Fuc alpha 1-3)GlcNAc(6S)beta 1-3Gal(6S)1-4GlcNAc(6S)-ol, Gal beta 1-4GlcNAc(6S)beta 1-6(Gal beta 1-3)GalNAc-ol, Gal beta 1-4GlcNAc(6S) beta1-6(NeuAc2-3Gal beta 1-3)Gal-NAc-ol, Gal beta 1-4GlcNAc(6S)beta 1-3Gal beta 1-4GlcNAc(6S)beta 1-6(Gal beta 1-3) GalNAc-ol, Gal(6S)beta 1-4GlcNAc-(6S)beta 1-6(Gal beta 1-3)GalNAc-ol, Gal beta 1-4GlcNAc(6S)beta 1-3Gal beta 1-4GlcNAc(6S)beta 1-6(NeuAc2-3Gal beta 1-3)-GalNAc-ol, Gal(6S)beta 1-4GlcNAc(6S)beta 1-6(NeuAc alpha 2-3Gal beta 1-3)GalNAc-ol, Gal(6S) beta 1-4GlcNAc-(6S)beta 1-3Gal beta 1-4GlcNAc(6S)beta 1-6(Gal beta 1-3)GalNAc- ol, Gal(6S)beta 1-4GlcNAc(6S)beta 1-3Gal beta 1-4GlcNAc-(6S)beta 1-6(NeuAc alpha 2-3Gal beta 1-3)GalNAc-ol, NeuAc alpha 2-6Gal beta 1-4GlcNAc(6S)beta 1-3Gal beta 1-4GlcNAc(6S)-ol, NeuAc alpha 2-3Gal beta 1-4GlcNAc(6S)beta 1-3Gal beta 1-4GlcNAc(6S)-ol, NeuAc alpha 2-6Gal beta 1-4GlcNAc(6S)beta 1-3Gal-(6S)beta 1-4GlcNAc(6S)-ol, NeuAc alpha 2-3Gal beta 1-4GlcNAc(6S)beta 1-3Gal(6S)beta 1-4GlcNAc(6S)-ol and Neu-Ac alpha 2-3Gal(6S)beta 1-4GlcNAc(6S)beta 1-3Gal(6S beta)1-4GlcNAc(6S)-ol. Proton chemical shifts for these oligosaccharides were assigned using one- and two-dimensional NMR spectroscopic methods. These results confirm the findings of Nakazawa et al. [Nakazawa, K., Ito, M., Yamagata, T. and Suzuki, S. (1989) in Keratan sulphate: chemistry, biology and chemical pathology (Greiling, H. and Scott, J.E., eds) pp. 99-110, The Biochemical Society, London], namely that keratanase II cleaves the O-glycosidic bond of a beta(1-3)-linked 6-O-sulphated N-acetylglucosamine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Oligosaccharides derived by keratanase II digestion of bovine articular cartilage keratan sulphates. 792 42

Receptor-bound growth factors elicit intracellular signals that lead to the phosphorylation and activation of numerous intracellular kinases and transcription factors with consequent changes in patterns of gene expression. Several oncogene products are able to mimic these signals, resulting in cell transformation and proliferation. For example, the introduction of oncogenic forms of Raf-1 kinase into fibroblasts induces transformation and leads to the constitutive expression of, among others, the c-fos proto-oncogene. Here it is shown that the elevation of c-fos promoter activity brought about by v-raf is mediated by TCF/Elk-1, which forms a ternary complex with SRF at the serum response element and is a substrate for mitogen-activating protein kinases in vitro. In NIH 3T3 fibroblasts, v-raf activates Erk2, and overexpression of an interfering mutant of Erk2 both blocks the ability of v-raf to activate the c-fos promoter and suppresses transformation. Mutation of individual mitogen-activating protein kinase phosphoacceptor sites in TCF/Elk-1 also compromises v-raf-activated expression of a Gal-Elk/Gal-chloramphenicol acetyltransferase reporter system. However, in at least one instance the introduction of glutamate, but not aspartate, at a phosphoacceptor site is compatible with activation. These results provide compelling evidence that phosphorylation of TCF/Elk-1 by Erk2 is a major link in the Raf-1 kinase-dependent signal transduction pathway that activates c-fos expression.
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PMID:Inhibition of v-raf-dependent c-fos expression and transformation by a kinase-defective mutant of the mitogen-activated protein kinase Erk2. 800 80

Two gangliosides were efficiently synthesized from asialo-GM1 (Gal beta 1-3GalNAc beta 1-4Gal beta 1-4Glc beta 1-1 Cer) and cytidine 5'-phosphate-N-acetylneuraminic acid (CMP-NeuAc) by using sialyltransferases in rat liver Golgi vesicles in vitro. These gangliosides were rapidly purified by a combination of anion exchange and reverse-phase column chromatographies. The ganglioside structures were determined by TLC analysis, treatment with a sialidase from Salmonella typhimurium LT2, which specifically hydrolyzes alpha 2-3 N-acetylneuraminic acid (NeuAc alpha 2-3) linkages, TLC immunostaining, and 1H-NMR spectroscopy. One of the gangliosides was identified as GD1 alpha [Neu-Ac alpha 2-3Gal beta 1-3(NeuAc alpha 2-6)GalNAc beta 1-4Gal beta 1-4Glc beta 1-1 Cer]. The other ganglioside was determined to be GM1b (NeuAc alpha 2-3Gal beta 1-3GalNAc beta 1-4Gal beta 1-4Glc beta 1-1 Cer), which has been reported in a previous study [Pohlentz, G., Klein, D., Schmitz, D., Schwarzmann, G., Peter-Katalinic, J. & Sandhoff, K. (1988) Biol. Chem. Hoppe-Seyler 369, 55-63]. Finally, GM1b and GD1 alpha were obtained from asialo-GM1 as a starting material in 8.1% and 1.2% overall yields, respectively. This study also suggests that the novel synthetic pathway asialo-GM1-->GM1b-->GD1 alpha may exist in rat liver.
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PMID:In vitro synthesis of disialoganglioside (GD1 alpha) from asialo-GM1 using sialyltransferases in rat liver Golgi vesicles. 816 48

Gal beta 1-->3GalN beta 1-->4Gal(3<--2 alpha Neu)beta 1-->4Glc beta-->1Sph (WILD20), a new glycosphingolipid, a breakdown product of the monosialoganglioside GM1 obtained through alkaline hydrolysis, shows dose-dependent platelet anti-aggregating properties in vitro and in vivo. This effect is agonist- and species-independent. The family of lysosphingolipids, to which the compound belongs, is present in platelets particularly after thrombin treatment. WILD20 antiplatelet effect is due to the interference with ADP or thrombin-induced aggregation, probably via phospholipase A2 (PLA2) blockade; the substance is also effective when arachidonic acid is used as an agonist. Serotonin blood levels are also reduced. The substance, orally active at dosages of 0.1-0.01 mg/kg as antiplatelets agent, prolonged bleeding time without interfering with the coagulative or fibrinolytic processes.
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PMID:Antiplatelet effects of a new de-N-acetyl-lyso-glycosphingolipid. 822 63

We evaluated the ability of a replication-deficient, recombinant adenoviral vector to transfer the bifunctional gene GAL-TEK, which expresses a marking/therapeutic gene product, to naturally occurring cat fibrosarcomas in situ. GAL-TEK contains an in-frame fusion of the bacterial LacZ gene for histochemical marking of tumors with beta-galactosidase (beta-Gal) and the HSV tk gene for enzyme-prodrug activation of the prodrug ganciclovir (GCV) to induce selective tumor cell killing. GAL-TEK bifunctional marking and cell killing activities were tested in vitro after adenoviral vector infection of HT1080 human fibrosarcoma cells. The tk activity of GAL-TEK is shown to be almost as potent as HSV tk to catalyze conversion of GCV to GCV nucleotides and promote selective cell killing. Using 8 cats with recurring 2.5-cm2 fibrosarcomas that either arose spontaneously or were induced by vaccine, we determined experimentally the administration routes and times required for optimum GAL-TEK gene transfer by beta-Gal histological staining and reverse transcriptase polymerase chain reaction to the multiple compartments of the growing fibrosarcomas consonant with minimizing collateral infection of neighboring tissues and other unwanted side effects.
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PMID:In vivo marking of spontaneous or vaccine-induced fibrosarcomas in the domestic house cat, using an adenoviral vector containing a bifunctional fusion protein, GAL-TEK. 852 80

To contribute to the possibility of studying in greater detail the biological significance of Sda-containing glycans as occur in Tamm-Horsfall glycoprotein, the following three spacer-linked tetrasaccharides have been synthesized: the Sda determinant alpha-Neu p5Ac-(2-->3)-[beta- D-GalpNAc-(1-->4)]-beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->O)(CH2)5NH 2 (1), the Gal-analogue alpha-Neup5Ac-(2-->3)-[beta-D-Galp-(1-->4)]-beta-D-Galp-(1-->4) -beta-D-GlcpNAc-(1-->O)(CH2)5NH2 (2), and the GlcNAc-analogue alpha-Neup5Ac-(2-->3)-[beta-D-GlcpNAc-(1-->4)]- beta-D-Galp-(1-->4)-beta-D-GlcpNAc-(1-->O)(CH2)5NH2 (3). The general trisaccharide acceptor 5-azidopentyl (methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy- D-glycero-alpha-D-galactonon-2-ulopyranosylonate)-(2-->3)-(2 ,6-di-O-benzyl- beta-D-galactopyranosyl)-(1-->4)-3,6-di-O- benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranoside was prepared, using methyl (phenyl 5- acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto- non- 2-ulopyranosid)- onate as the sialyl donor. For the syntheses of 1, 2, and 3 the glycosyl donors 3,4,6-tri-O- acetyl-2-deoxy-2-phthalimido-alpha-D-galactopyranosyl bromide, 2,3,4,6-tetra-O-acetyl-alpha-D- galactopyranosyl bromide, and 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido -beta-D-glucopyranosyl trichloroacetimidate, respectively, proved to be the most suitable.
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PMID:Synthesis of the Sda determinant and two analogous tetrasaccharides. 916 97

Factors that may improve retroviral transduction of primitive human hematopoietic cells were studied using MFG-based vectors containing a LacZ gene and produced either by a murine (psi-Crip) or a human (Tasaf) cell line. Cord blood (CB) or bone marrow (BM) CD34+ cells were stimulated and transduced in the presence of three cytokines (interleukin 3 [IL-3], IL-6, and stem cell factor [SCF; c-Kit Ligand]). In the supernatant infection protocol, hematopoietic progenitor cells as measured by X-Gal staining of colony-forming unit cells (CFU-Cs) were transduced more effectively with Tasaf (20%) than with psi-Crip (8%). In contrast, there was no difference between these two cell lines in a coculture protocol. However, gene transfer into more primitive CD34+CD38- subsets and in LTC-IC-derived colonies was low. The use of a large number of cytokines including FLT3-L and PEG-rhMGDF increased the transduction efficiency into CD34+CD38(-)-derived CFU-Cs (35% by PCR) or LTC-ICs (10%). A virus pseudotyped with gibbon ape leukemia virus (GALV) envelope further improved gene transfer to 60 and 48% for LacZ+ CFU-C- and LTC-IC-derived colonies, respectively. These conditions of transduction allowed multilineage engraftment of primitive cord blood cells in NOD-SCID mice. Moreover, 10% (at least) of the human hematopoietic cells recovered from the marrow of these immunodeficient animals were transduced. These data suggest that the efficiency of transduction of human hematopoietic primitive cells can be significantly improved by judicious combinations of recombinant cytokines and high retroviral titers.
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PMID:Retrovirus-mediated gene transfer into human CD34+38low primitive cells capable of reconstituting long-term cultures in vitro and nonobese diabetic-severe combined immunodeficiency mice in vivo. 968 21

A lectin was isolated from the mycelium of the stationary growing enthomopathogenic fungus Beauveria bassiana by extraction, chromatography on QAE-Sephadex A-25, salt precipitation, and hydrophobic chromatography on Phenyl-Sepharose 4B. The Beauveria bassiana lectin (BBL) is a 15 kDa glycoprotein rich in hydrophobic amino acids, without detectable amount of methionine. It contains 12.6% of carbohydrates including galactose and mannose. Isoelectric point was found at pH 7.1. The lectin is stable between pH 6 and 11, and at temperature under 50 degrees C. The activity of the lectin was not dependent on with Ca++, Mn++, Mg++ cations and was apparently not blood group ABO specific. The hemagglutination caused by the lectin was inhibited by alpha lactose (Gal beta 1-->4 Glc alpha), but not by beta lactose (Gal beta 1-->4 Glc beta). In direct ELISA the BBL preferentially reacted with some glycoproteins carrying O-linked sugar structure Gal beta 1-->3 GalNAc: strongly with human glycophorin A and weaker with mouse glycophorin, fetuin, IgA, ovine submaxillary mucin. On the other hand BBL did not react in direct ELISA with N-glycoproteins (alpha 1-acid glycoprotein, haptoglobin, fibronectin), however, N-glycoproteins could act as inhibitors of lectin-glycophorin A interaction. We observed also weak interaction with asialo-Tamm-Horsfall N-glycoprotein having unusual large, branched N-glycans with outer GalNAc beta 1-->4Gal sequence. Moreover, the interaction of BBL with highly sialylated preparations of glycoproteins was weaker than with asialo forms. Presented results indicate that BBL exhibits sugar binding specificity towards glycotope corresponding to Thomsen-Friedenreich antigen and its related sequences: Gal beta 1-->3 GalNAc > Neu Ac alpha 2-3 Gal beta 1-->3 (Neu Ac alpha 2-6) GalNAc > Gal beta 1-->4 Glc alpha.
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PMID:Lectin from Beauveria bassiana mycelium recognizes Thomsen-Friedenreich antigen and related structures. 1042 10

Genetic and cell culture analyses have shown that the development of melanocytes from neural crest-derived precursor cells critically depends on the tyrosine kinase receptor KIT and the basic-helix-loop-helix-leucine zipper transcription factor MITF. KIT and MITF show complex interactions in that MITF is needed for the maintenance of Kit expression in melanoblasts and KIT signaling modulates MITF activity and stability in melanocyte cell lines. Using primary neural crest cell cultures from embryos homozygous for a Kit null allele marked by an inserted LacZ gene (Kit(W-LacZ)), we show that the onset of Mitf expression in melanoblasts does not require KIT. In fact, provided that the melanocyte growth factor endothelin-3 is present, a small number of MITF/beta-Gal-positive cells can be maintained for at least 2 weeks in Kit(W-LacZ)/Kit(W-LacZ) cultures. These cells express several pigment cell-specific genes that are thought or have been shown to be activated by MITF, including dautochrome tautomerase, pMel 17/Silver and tyrosinase-related protein-1, but lack expression of the MITF target gene tyrosinase, which encodes the rate-limiting enzyme in melanin synthesis. Consequently, the cells remain unpigmented. Addition of cholera toxin, which elevates cAMP levels and mimics part of the KIT signaling pathway, increases the number of MITF-positive cells in Kit(W-LacZ)/Kit(W-LacZ) cultures, leads to tyrosinase expression, and induces the differentiation of melanoblasts into mature, pigmented melanocytes. Even when added on day 5-6 of culture, cholera toxin still rescues tyrosinase expression and differentiation. The results thus demonstrate that the presence of MITF is not sufficient for tyrosinase expression in melanoblasts and that KIT signaling influences gene expression during melanocyte development in a gene-selective manner.
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PMID:Signaling and transcriptional regulation in the neural crest-derived melanocyte lineage: interactions between KIT and MITF. 1107 59


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