Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The Mr 185,000 glycoprotein encoded by human c-erbB-2/neu/HER2 gene, termed c-erbB-2 gene product, shows a close structural similarity with epidermal growth factor receptor and is now regarded to be a growth factor receptor for an as yet unidentified ligand. Abundant c-erbB-2 mRNA was demonstrated by Northern blot studies in the human breast cancer cell line SK-BR-3. Cellular radiolabeling experiments followed by immunoprecipitation with three different anti-c-erbB-2 gene product antibodies, recognizing extracellular domain, kinase domain, and carboxyl-terminal portion, respectively, demonstrated the production of a large amount of c-erbB-2 gene product which had the capacity to be phosphorylated. Immunization of mice with concentrated culture medium conditioned by SK-BR-3 cells always generated antibodies against c-erbB-2 gene product, demonstrating that this culture medium contained substance(s) immunologically indistinguishable from c-erbB-2 gene product. This observation was supported by the successful development of a monoclonal antibody against c-erbB-2 gene product, GFD-OA-p185-1, by immunizing mice with this culture medium. The biochemical nature of the substance(s) present in the culture medium was further characterized. When the culture medium conditioned by [35S]cysteine-labeled SK-BR-3 cells was immunoprecipitated by three different anti-c-erbB-2 gene product antibodies, only the antibody recognizing extracellular domain precipitated the [35S]-labeled protein with a molecular weight of 110,000, namely p110. The newly developed monoclonal antibody also immunoprecipitated this protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The presence of c-erbB-2 gene product-related protein in culture medium conditioned by breast cancer cell line SK-BR-3. 198 Nov 43

Two monoclonal antibodies against the receptor for platelet-derived growth factor (PDGF) were obtained by immunizing mice with pure PDGF receptor preparations derived from porcine uterus. The antibodies, denoted PDGFR-B1 and PDGFR-B2, both bound to the external domain of the receptor, as demonstrated by indirect immunofluorescence and binding of 125I-labeled antibodies to intact human fibroblasts. Both antibodies precipitated pure 175-kDa 32P-labeled autophosphorylated porcine PDGF receptor as well as a Mr 175,000 glycoprotein from metabolically labeled cells. The monoclonal antibodies did not inhibit binding of 125I-PDGF to human fibroblasts and did not stimulate these cells to undergo mitosis. Both antibodies induced clustering and down-regulation of their antigen. However, this resulted in only a partial loss of cell surface binding sites for PDGF itself, consistent with the conclusion that the monoclonals recognized only one of two or several receptors for PDGF. Clustering and down-regulation were not seen when the cells were incubated with monovalent Fab' fragments of the PDGFR-B2 antibody. The antibodies also stimulated autophosphorylation of pure PDGF receptor, and PDGFR-B2 was shown to stimulate phosphorylation of phosphofructokinase, an exogenous substrate for the PDGF receptor kinase. High concentrations of PDGFR-B2 antibody, or Fab' fragments thereof, failed to enhance the PDGF receptor kinase activity, compatible with the possibility that dimerization was of importance in the antibody-stimulated kinase activity of purified PDGF receptors.
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PMID:Characterization of two monoclonal antibodies reactive with the external domain of the platelet-derived growth factor receptor. 245 16

We have previously reported that the amino acid sequence of the common acute lymphoblastic leukemia antigen (CALLA, CD10) translated from a normal human kidney cDNA clone is identical to that of neutral endopeptidase (NEP, EC 3.4.24.11). In this study, we show that by flow cytometry, a monoclonal antibody (135A3) produced against rabbit NEP reacted selectively with leukemia and melanoma cell lines expressing CALLA on their surface. A glycoprotein of apparent Mr 100,000 was immunoprecipitated from surface labeled NALM-1 leukemia or Mel-1477 melanoma cells with monoclonal antibodies to NEP (135A3) or CALLA (44C10). mRNAs hybridizing to a NEP-specific probe were present in CALLA+ leukemia and melanoma cell lines, but absent from CALLA- lines. NEP enzymatic activity was detected on intact cells from CALLA+ lines, but not CALLA- lines. The activity was blocked by two selective inhibitors of NEP, thiorphan and phosphoramidon. CALLA antigen purified from the NALM-6 leukemic cell line by affinity to 44C10-IgG Sepharose retained a peptidase activity that was completely blocked by thiorphan and phosphoramidon. Thus the CALLA antigen present at the surface of leukemia and melanoma cell lines is an enzymatically active neutral endopeptidase.
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PMID:Common acute lymphoblastic leukemia antigen expressed on leukemia and melanoma cell lines has neutral endopeptidase activity. 252 92

A panel of seven murine monoclonal antibodies reactive with human hepatocellular carcinoma (HCC) cell line, SK- HEP-1, resulted in the definition of four distinct antigen systems, designated HB4, HB5, HB1 and HJ2. HB4 antigen was found to be expressed specifically on HCC cell lines and fresh HCC specimens but not on normal liver. Immunoprecipitation tests suggest that the HB4 epitope may be a heat-stable carbohydrate determinant on a high molecular mass molecule. HB5 antigen was found to have less-restricted expression on a panel of normal adult tissues and on melanoma, astrocytoma, sarcoma, neuroblastoma and epithelial cancer cell lines. In fetal and adult liver, HB5 antigen localized to bile canaliculi and ducts. Under reducing conditions, three mAbs detected a Mr 140,000 glycoprotein using lysates of [125-I], [3-H]-glucosamine and [35-S]-methionine labeled SK-HEP-1 cells. Under non-reducing conditions an additional component of greater than Mr 200,000 was also detected. HB1 antigen was found on almost all monolayer cell lines and not on most cultured suspension cells. This antigen was also detected on cultured HCC cells inoculated into nu/nu mice. Immunoprecipitation experiments revealed that the HB1 antigen is a bimolecular complex with an Mr 170,000 alpha chain and Mr 130,000 beta chain under non-reducing conditions, and three subunits of Mr 140,000, Mr 30,000 and Mr 130,000 under reducing conditions. Two antibodies reacted with epitopes on the alpha chain. HJ2 antigenic determinant is a heat-stable component which could not be immunoprecipitated. This most widely expressed antigen was found in secreted form in many of the cells and tissues examined. These antibodies introduce new antigens which may serve as useful markers for the diagnosis, classification and investigation of HCC and other liver diseases.
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PMID:Serological analysis and biochemical characterization of monoclonal antibodies defining antigens of human hepatocellular carcinoma. 255 3

A testis-specific gene Tpx-1, located between Pgk-2 and Mep-1 on mouse chromosome 17, was isolated from a cosmid clone, and its cDNA sequences were determined. The predicted coding sequence of Tpx-1 isolated from BALB/c mice showed 64.2% nucleotide and 55.1% amino acid sequence similarity with that of a rat sperm-coating glycoprotein gene, the protein product of which is secreted by the epididymis. To examine the evolutionary relationship between Tpx-1 and a sperm-coating glycoprotein gene, the cDNA sequence of TPX1, the human counterpart of Tpx-1, was determined. The comparison of the predicted coding sequences of Tpx-1 and TPX1 showed 77.8% nucleotide and 70% amino acid sequence similarity. Since Tpx-1 (from mouse) is more similar to TPX1 (from man) than it is to a rat sperm-coating glycoprotein gene, we conclude that Tpx-1 (TPX1) and a sperm-coating glycoprotein gene are closely related, but distinct, genes belonging to the same gene family. The predicted Tpx-1 protein of a t mutant mouse CRO437 differs from that of BALB/c mice by one amino acid insertion in the putative signal peptide. TPX1 was mapped to 6p21-qter by Southern blot analysis of interspecies somatic hybrid cell lines.
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PMID:Cloning and mapping of a testis-specific gene with sequence similarity to a sperm-coating glycoprotein gene. 261 36

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

A gene coding for the Tac protein (interleukin-2 receptor alpha-subunit, IL-2R alpha) of the interleukin-2 receptor was constructed by chemoenzymatic gene synthesis. The gene designed for mutagenesis codes for a receptor protein where all 10 methionines are substituted by alanine, valine, leucine, and isoleucine. In addition, aspartate at position 6 is substituted by glutamate. This desmethionine IL-2R alpha and the wild-type IL-2R alpha genes were integrated into a eukaryotic expression vector and transferred into different cell lines. The recipient cell lines express both wild-type and mutant receptor proteins on their cell surfaces which are recognized equally by different monoclonal antibodies. It was possible to establish cell lines with high level IL-2R alpha chain expression by fluorescence-activated cell sorting. The wild-type IL-2R alpha expressed in LTK- cells is a glycoprotein with an apparent molecular size of about 60 kDa and a typical low interleukin-2 binding affinity of KD = 12 nM. Despite the fact that 11 amino acids are altered, no significant difference in the mutant IL-2R alpha is observed, exhibiting the same molecular size and a low interleukin-2 binding affinity of KD = 26 nM.
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PMID:Expression and characterization of a des-methionine mutant interleukin-2 receptor (Tac protein) with interleukin-2 binding affinity. 313 42

The neu oncogene (also referred to as c-erbB-2 and HER2) encodes a 185-kDa transmembrane glycoprotein with tyrosine kinase activity termed p185. The p185 glycoprotein is structurally related to the epidermal growth factor receptor. It is thought that p185 is the receptor for an as yet unidentified growth factor. In the present study, RNA blot analyses and immunohistochemical studies were performed on rat tissues obtained from a variety of prenatal and postnatal stages to examine the expression of the neu oncogene and its product, p185, during normal development. Expression of the neu gene was detected in mid-gestation embryos in a variety of tissues including nervous system, connective tissue, and secretory epithelium, but not in lymphoid tissue. In adult animals, secretory epithelial tissues and basal cells of the skin expressed neu. These studies demonstrate that the neu gene is expressed in a tissue- and developmental stage-specific manner. We suggest that the p185 molecule plays an important role in the growth and development of a variety of tissues, and, in particular, in epithelial tissue.
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PMID:Stage- and tissue-specific expression of the neu oncogene in rat development. 331 11

Lectin and rhodopsin antibody binding sites were studied in developing and adult rat photoreceptors in order to compare changes in the total carbohydrate pool with the movement of a known glycoprotein rhodopsin. Electron microscope immunocytochemical techniques utilizing modified colloidal gold methods were used. At birth, all three lectins - Concanavalin A (ConA), Ricinus communis agglutinin II (RCA II) and wheat germ agglutinin (WGA) - showed heavy labelling of the photoreceptor surface scleral to the outer limiting membrane. At the same age, a monoclonal antibody against rhodopsin, RET-P1, revealed sparse labelling of only occasional immature photoreceptor surfaces. At postnatal day 4(P4), all three lectins showed variable binding to the inner segment and along the length of the newly forming connecting cilium. There was generally a region of more intense label at the base of the cilium. RET-P1 binding to P4 retina showed a discontinuous distribution, with heavily labelled inner segments being adjacent to unlabelled inner segments. This pattern indicates that the initial expression of rhodopsin is not a coordinate event but occurs in discrete cells, possibly related to the end of mitosis. RET-P1 binding at this age was reduced or absent from the proximal connecting cilium. AT P7, when the outer segments are beginning to develop, all the lectins and RET-P1 showed reduced binding to the inner segment plasma membrane and heavy labelling of the outer segment surface. In favourable sections, heavy labelling of the photoreceptor cell body plasma membrane by ConA and RCA II was also observed, terminating abruptly at the outer limiting membrane. The variation in ligand binding between different cellular compartments which are all formed from a continuous plasma membrane may indicate the presence of special barriers to diffusion of membrane components. This labelling pattern persisted into maturity. RET-P1 and lectin binding did not always correspond in developing retina, indicating that at least part of the observed lectin label must be due to other glycoproteins or glycolipids. Post-embedding thin section labelling of adult rat retina revealed a uniform binding pattern across the outer segment for ConA, WGA and RET-P1. However, RCA II exhibited labelling only along the basal edge of outer segments. Labelling of isolated, opened discs from bovine rod outer segments revealed binding to a single surface for ConA, WGA and RET-P1, but RCA II only labelled a small amount of membrane. Hence RCA II seems to recognize a determinant present only on the outer segment plasma membrane.
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PMID:Lectin and antibody labelling of developing rat photoreceptor cells: an electron microscope immunocytochemical study. 375 63

A major egg glycoprotein (MEG) was purified from a crude soluble extract of Schistosoma mansoni ova (Egyptian strain) by successive steps of lectin affinity and ion-exchange chromatography. Radioiodinated MEG exhibited a single precipitation band upon immunodiffusion against antiserum from chronically infected mice, and ran as a single band on PAGE (Rf 0.38) and SDS-PAGE (Rf 0.36). Its estimated m.w. was 70,000. The degree of stage and species specificity of MEG and the effect of various treatments on its serologic reactivity were determined by radioimmunoassay (RIA). A low degree of cross-reactivity between MEG and similarly prepared soluble antigens from adult worms and cercariae was demonstrated by RIA inhibition tests, whereas a high degree of cross-reactivity was found between MEG and a crude soluble S. haematobium egg antigen. In similar RIA inhibition tests, the Puerto Rican S. mansoni had a lower degree of cross-reactivity with S. haematobium than the Egyptian strain. MEG was four times more abundant in SEA from a Puerto Rican strain of S. mansoni than in SEA from the Egyptian strain. The serologic reactivity of MEG was stable to heat at 100 degrees C for 60 min, to 0.1 N NaOH or HCl, and to 10% TCA. Treatment of MEG with pronase caused a limited fragmentation of the molecule and some loss of its serologic reactivity. Periodate oxidation resulted in a substantial loss of molecular mass and of serologic reactivity, leaving a low residual activity that is only partially cross-reactive with the bulk of MEG. These results suggest the importance of both carbohydrate and peptide moieties of MEG for its serologic reactivity.
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PMID:Characterization of a purified glycoprotein from Schistosoma mansoni eggs: specificity, stability, and the involvement of carbohydrate and peptide moieties in its serologic activity. 617 18


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