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)

This work is part of an investigation into G. I. mucin susceptibility to enzyme degradation in normal and disease states. Formalin-fixed/paraffin embedded foetal (14-23 weeks) and neonatal colonic tissue was stained for mucins (neutral, N- and O-acylated sialomucins and sulphomucins) and PNA, UEA1, and Limax flavus. Enzymes tested: neuraminidases, alpha- and beta-galactosidase (E. coli and B. testis), beta-N-acetyl-glucosaminidase, alpha-fucosidase, single or in sequence, with and without prior neuraminidase treatment and followed by the stains. Acid mucins predominate throughout foetal life, sulphation occurs at 14 weeks and O-acylated sialomucins at 23 weeks. PNA and UEA1 are seen in traces or not detected. The mucin profile at birth is similar to the adult. Colonic mucins are susceptible to neuraminidase which abolishes Limax staining. The glycosidases effect on PNA is seen only with prior neuraminidase treatment and is particularly marked with beta-Gal(BT) in Neu----beta-Gal----beta-N-AcetylGlc than with beta-Gal (EC). Fucosidase with prior neuraminidase treatment has effect on UEA1 (decreases) and PNA (increases) affinities. Neuraminidase is essential as a first step in the process and by using beta-galactosidases EC and BT it was possible to show different PNA binding affinities. Preliminary data demonstrate the feasibility of this histochemical approach to the study of colonic mucins and forms the basis for further studies in the adult.
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PMID:Goblet cell mucin in human foetal colon, its composition and susceptibility to enzyme degradation: a histochemical study. 264 9

Carbon-13 NMR spectroscopic studies of native and sequentially deglycosylated ovine submaxillary mucin (OSM) have been performed to examine the effects of glycosylation on the conformation and dynamics of the peptide core of O-linked glycoproteins. OSM is a large nonglobular glycoprotein in which nearly one-third of the amino acid residues are Ser and Thr which are glycosylated by the alpha-Neu-NAc(2-6)alpha-GalNAc- disaccharide. The beta-carbon resonances of glycosylated Ser and Thr residues in intact and asialo mucin display considerable chemical shift heterogeneity which, upon the complete removal of carbohydrate, coalesces to single sharp resonances. This chemical shift heterogeneity is due to peptide sequence variability and is proposed to reflect the presence of sequence-dependent conformations of the peptide core. These different conformations are thought to be determined by steric interactions of the GalNAc residue with adjacent peptide residues. The absence of chemical shift heterogeneity in apo mucin is taken to indicate a loss in the peptide-carbohydrate steric interactions, consistent with a more relaxed random coiled structure. On the basis of the 13C relaxation behavior (T1 and NOE) the dynamics of the alpha-carbons appear to be unique to each amino acid type and glycosylation state, with alpha-carbon mobilities decreasing in the order Gly greater than Ala = Ser greater than Thr much greater than monoglycosylated Ser/Thr approximately greater than disaccharide linked Ser/Thr.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of glycosylation on the conformation and dynamics of O-linked glycoproteins: carbon-13 NMR studies of ovine submaxillary mucin. 277 22

Purified human colonic mucin contains six distinct components which may be separated by DEAE-cellulose chromatography. Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. The late eluting mucin species VI contained at least five discrete neutral oligosaccharides and six major acidic structures. While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. These studies demonstrate that human colonic mucin possesses species with characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures.
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PMID:Oligosaccharide structures of isolated human colonic mucin species. 406 81

The carbohydrate structure and complete amino acid sequence of a human lambda-type immunoglobulin light chain, protein Sm lambda has been determined. The protein was isolated from the urine of a patient with a plasma cell dyscrasia resembling gamma-heavy-chain disease. 13 tryptic peptides covering the entire polypeptide chain of 135 residues were isolated from the aminoethylated protein, and 15 chymotryptic peptides, accounting for 131 residues, were recovered from the carboxymethylated protein. The sequence of 18 of these peptides was partially or completely determined by the Edman-dansyl technique or C-terminal analysis, permitting the establishment of the complete primary structure of the polypeptide chain. The sequences established that this light chain possessed an intramolecular deletion of 81 amino acid residues. The N-terminal 30 residues showed considerable homology with other lambda chains of subgroup II. The defect began at position 31, in the first hypervariable region, and encompassed the remainder of the variable region through position 109. The constant region was fully intact and normal synthesis recommenced with a glutaminyl residue at position 110, the first residue of the constant region. This light chain contained carbohydrate in the hypervariable region just preceding the deletion. The precise number and locations of the oligosaccharide chains were established by amino acid sequence analysis of glycopeptides isolated from proteolytic hydrolysates by chromatography on Bio-Gel P-6 columns. These studies showed that protein Sm lambda contains one N-glycosidically-linked chain attached to asparagine-25 and one O-glycosidically-linked oligosaccharide chain attached to serine-21. The structures of the oligosaccharide chains were determined by methylation analysis, gas chromatography and hydrolysis with specific glycosidases. The structure of the N-glycosidically-linked chain was NeuAc(alpha 2 leads to 6)Gal(beta 1 leads to 4)GlcNAc(beta 1 leads to 2)Man(alpha 1 leads to 6)[NeuAc(alpha 2 leads to 6)Gal(beta 1 leads to 4)GlcNAc(beta 1 leads to 2)Man(alpha 1 leads to 3)]Man(beta 1 leads to 4)GlcNAc(beta 1 leads to 4)[Fuc alpha 1 leads to 6]GlcNAc leads to Asn. The second O-glycosidically-linked chain was a disialylated tetrasaccharide with the structure, Neu(alpha 2 leads to 3)Gal(beta 1 leads to 3)[NeuAc(alpha 2 leads to 6)GalNAc leads to Ser. This mucin-type disialylated tetrasaccharide in close proximity to N-asparagine-linked chains has not been previously observed in the oligosaccharide chains of immunoglobulins.
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PMID:Localization of the carbohydrate units in a human immunoglobulin light chain, protein Sm lambda. 678 88

Among mushrooms of Pleurotus cornucopiae two kinds of fruit bodies, lectin (PCL)-containing and -deficient, were found. The PCL-deficient fruit body was found to contain a 16.5-kDa protein, which was purified to homogeneity and crystallized. Properties of the protein were investigated in comparison with PCL. The protein consisted of four identical subunits each having a molecular mass of 16.5 kDa, which was close to that of PCL. Partial amino acid sequences of the two proteins were analyzed and some sequence homology was found, although the protein did not cross-react with anti-PCL serum and it was devoid of binding activity for mucin, an inhibitor of PCL. The 16.5-kDa protein was not found in vegetatively growing mycelia, indicating that the synthesis of the protein was developmentally regulated as was PCL. The results suggest that the 16.5-kDa protein was related to PCL.
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PMID:Isolation, crystallization, and characterization of a 16.5-kDa protein from fruit bodies of a lectin-deficient strain of Pleurotus cornucopiae. 776 90

Two human diffuse gastric carcinoma cell lines were established in vitro from xenografted tumours serially passaged in nude mice. Of 12 primary diffuse gastric carcinomas, 7 were successfully xenografted in nude mice (58.3%). Short-term primary cultures were achieved in all the xenografted lines. However, only 2 of the 7 short-term primary cultures were established as long-term cultures (GP202 and GP220). GP202 cells are larger than GP220 cells, show less abundant intercellular junctions at the ultrastructural level and grow in culture as a compact thin monolayer. The GP220 cells grow preferentially in small clusters attached to the monolayer, with a subpopulation of floating cells. Both lines have cells containing small mucin vacuoles in the cytoplasm and cells displaying a typical signet-ring shape. GP202 cells grow as solid tumours in nude mice but GP220 cells do not give rise to tumours. The flow cytometry and karyotype analysis showed aneuploidy in GP202 cells, with many numerical and structural chromosomal abnormalities, and diploidy in GP220 cells, with several structural chromosomal abnormalities. The CDw75 and Tn antigens are more prominently expressed in GP202 cells than in GP220 cells. T antigen is only expressed in GP202 cells, whereas only GP220 cells express EGFR. Sialosyl-Tn is not expressed in either of the cell lines. The gastric cancer cell lines described in this paper represent a valuable addition to the small number of diffuse gastric cancer cell lines currently available and also provide a good model for further in vitro and in vivo studies of gastric carcinogenesis.
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PMID:Establishment and characterization of two cell lines derived from human diffuse gastric carcinomas xenografted in nude mice. 892 30

The abilities of isolates of saprophytes (Neurospora crassa, Aspergillus nidulans), an opportunistic human pathogen (Aspergillus fumigatus), an opportunistic insect pathogen (Aspergillus flavus), plant pathogens (Verticillium albo-atrum, Verticillium dahliae, Nectria haematococca), a mushroom pathogen (Verticillium fungicola) and entomopathogens (Verticillium lecanii, Beauveria bassiana, Metarhizium anisopliae) to utilize plant cell walls and insect cuticle components in different nutrient media were compared. The pathogens showed enzymic adaptation to the polymers present in the integuments of their particular hosts. Thus, the plant pathogens produced high levels of enzymes capable of degrading pectic polysaccharides, cellulose and xylan, as well as cutinase substrate, but secreted little or no chitinase and showed no proteolytic activity against elastin and mucin. The entomopathogens and V. fungicola degraded a broad spectrum of proteins (including elastin and mucin) but, except for chitinase, cellulase (V. lecanii and V. fungicola only) and cutinase (B. bassiana only), produced very low levels of polysaccharidases. The saprophytes (Neu. crassa and A. nidulans) and the opportunistic pathogens (A. fumigatus and A. flavus) produced the broadest spectrum of protein and polysaccharide degrading enzymes, indicative of their less specialized nutritional status. V. lecanii and V. albo-atrum were compared in more detail to identity factors that distinguish plant and insect pathogens. V. albo-atrum, but not V. lecanii, grew well on different plant cell wall components. The major class of proteases produced in different media by isolates of V. albo-atrum and V. dahliae were broad spectrum basic (pI > 10) trypsins which degrade Z-AA-AA-Arg-NA substrates (Z, benzoyl; AA, various amino acids; Na, nitroanilide), hide protein azure and insect (Manduca sexta) cuticles. Analogous peptidases were produced by isolates of V. lecanii and V. fungicola but they were specific for Z-Phe-Val-Arg-NA. V. albo-atrum and V. dahliae also produced low levels of neutral (pI ca 7) and basic (pI ca 9.5) subtilisin-like proteases active against a chymotrypsin substrate (Succinyl-Ala2-Pro-Phe-NA) and insect cuticle. In contrast, subtilisins comprised the major protease component secreted by V. lecanii and V. fungicola. Both V. lecanii and V. albo-atrum produced the highest levels of subtilisin and trypsin-like activities during growth on collagen or insect cuticle. Results are discussed in terms of the adaptation of fungi to the requirements of their ecological niches.
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PMID:Adaptation of proteases and carbohydrates of saprophytic, phytopathogenic and entomopathogenic fungi to the requirements of their ecological niches. 920 74

A better understanding of immune recognition of cells has led to identification of potential new targets on tumor cells. Noticeable successes in melanoma have been immunization with the GM2 ganglioside vaccine, and the identification of novel antigens such as MAGE, BAGE and GAGE recognized by T cells cloned from cancer patients with regressing disease. However, the unexpected finding that other antigens recognized by these T cells were overexpressed normal differentiation antigens such as tyrosinase. Pmel 17 and Melan A have led to vaccines developed against differentiation antigens expressed in other solid tumors. Monoclonal antibody, anti-idiotype and antigen based vaccines for colorectal target antigens 17-1A, CEA and 791Tgp72 are all in clinical development. Similarly HER2/neu and mucin overexpression in breast cancer represent promising targets. Mutations in tumor oncogenes or suppressor genes which lead to malignant transformation can also present tumor-specific antigens. The most effective vaccines against infectious disease are live viruses. The development of DNA vaccines which act like viruses in entering cells and show continuous production of antigens offers great potential for the future.
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PMID:Cancer vaccines. 939 16

Prostatic adenocarcinoma with a signet ring cell (SRC) component is a rare, incompletely characterized variant that must be distinguished from similar tumors of bladder or gastric origin. In this study, we used mucin and immunoperoxidase stains on formalin-fixed, paraffin-embedded sections from 12 prostatic adenocarcinomas with SRC components, with antibodies to prostate-specific antigen (PSA), cytokeratins, MIB-1, bcl-2, c-MET, CD44v6, and CD44v7; we performed a comparison study on six bladder and seven gastric carcinomas with SRCs. The prostatic SRC component was always associated with the usual high-grade adenocarcinoma. Both components were positive for PSA, AE1/AE3, and CAM 5.2 (12 cases of 12) and also expressed c-MET (5 cases of 9), CD44v6 (9 of 10), and CDv7 (9 of 10). Only rare cells stained for bcl-2 (3 cases of 9). The mean MIB-1 proliferation index was 8%. Intracellular mucin was identified (periodic acid-Schiff with diastase predigestion (PAS-D) in 9 cases of 10, mucicarmine in 5 of 10, alcian blue in 6 of 10). Bladder and gastric tumors were positive for PSA (3 cases of 6 and 2 of 7, respectively), using a polyclonal antibody, and for bcl-2 (5 cases of 6, 2 of 7), c-MET (6 of 6, 6 of 7), CD44v6 (5 of 6, 6 of 7), and CD44v7 (4 of 6, 4 of 7), with mean MIB-1 proliferation indices of 15 and 35%, respectively. All were negative for cytokeratin 34 beta E12. We conclude that prostatic adenocarcinomas with SRC components are typically accompanied by high-grade adenocarcinoma; are variably positive for mucin, with PAS-D being the most sensitive stain; show expression of PSA, cytokeratins, MIB-1, bcl-2, c-MET, and CD44 similar to that shown by high-grade adenocarcinoma components; have a low MIB-1 proliferation index; and are not always distinguishable from SRC components of bladder and stomach carcinomas with any of the above stains, including PSA.
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PMID:Prostatic carcinoma with signet ring cells: a clinicopathologic and immunohistochemical analysis of 12 cases, with review of the literature. 964 93

CD164 is a novel 80- to 90-kD mucin-like molecule expressed by human CD34(+) hematopoietic progenitor cells. Our previous results suggest that this receptor may play a key role in hematopoiesis by facilitating the adhesion of CD34(+) cells to bone marrow stroma and by negatively regulating CD34(+) hematopoietic progenitor cell growth. These functional effects are mediated by at least two spatially distinct epitopes, defined by the monoclonal antibodies (MoAbs), 103B2/9E10 and 105A5. In this report, we show that these MoAbs, together with two other CD164 MoAbs, N6B6 and 67D2, show distinct patterns of reactivity when analyzed on hematopoietic cells from normal human bone marrow, umbilical cord blood, and peripheral blood. Flow cytometric analyses revealed that, on average, 63% to 82% of human bone marrow and 55% to 93% of cord blood CD34(+) cells are CD164(+), with expression of the 105A5 epitope being more variable than that of the other identified epitopes. Extensive multiparameter flow cytometric analyses were performed on cells expressing the 103B2/9E10 functional epitope. These analyses showed that the majority (>90%) of CD34(+) human bone marrow and cord blood cells that were CD38(lo/-) or that coexpressed AC133, CD90(Thy-1), CD117(c-kit), or CD135(FLT-3) were CD164(103B2/9E10)+. This CD164 epitope was generally detected on a significant proportion of CD34(+)CD71(lo/-) or CD34(+)CD33(lo/-) cells. In accord with our previous in vitro progenitor assay data, these phenotypes suggest that the CD164(103B2/9E10) epitope is expressed by a very primitive hematopoietic progenitor cell subset. It is of particular interest to note that the CD34(+)CD164(103B2/9E10)lo/- cells in bone marrow are mainly CD19(+) B-cell precursors, with the CD164(103B2/9E10) epitope subsequently appearing on CD34(lo/-)CD19(+) and CD34(lo/-)CD20(+) B cells in bone marrow, but being virtually absent from B cells in the peripheral blood. Further analyses of the CD34(lo/-)CD164(103B2/9E10)+ subsets indicated that one of the most prominent populations consists of maturing erythroid cells. The expression of the CD164(103B2/9E10) epitope precedes the appearance of the glycophorin C, glycophorin A, and band III erythroid lineage markers but is lost on terminal differentiation of the erythroid cells. Expression of this CD164(103B2/9E10) epitope is also found on developing myelomonocytic cells in bone marrow, being downregulated on mature neutrophils but maintained on monocytes in the peripheral blood. We have extended these studies further by identifying Pl artificial chromosome (PAC) clones containing the CD164 gene and have used these to localize the CD164 gene specifically to human chromosome 6q21.
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PMID:CD164, a novel sialomucin on CD34(+) and erythroid subsets, is located on human chromosome 6q21. 968 Mar 53


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