Disease relevance of glycoprotein

• We have isolated and sequenced clones encoding the repeated subunit of the surface-associated glycoprotein gp15/400 from the two nematode species predominantly responsible for lymphatic filariasis in humans: Brugia malayi and Wuchereria bancrofti [1].
• Characterisation of an immunodominant glycoprotein antigen of Onchocerca volvulus with homologues in other filarial nematodes and Caenorhabditis elegans [2].
• Infected wild-type mice demonstrated significant goblet cell hyperplasia and increased mucin glycoprotein [3].
• The defect in the laminin-alpha2 chain, a direct ligand to the dystrophin-glycoprotein complex, causes a form of muscular dystrophy which affects infants [4].
• Proteomics computational analyses indicate that the carboxyl terminal glycoprotein (Gc) encoded by Sandfly fever virus (SAN), a phlebovirus, has a significant amino acid sequence similarity with envelope protein 1 (E1), the class II fusion protein of Sindbis virus (SIN), an Alphavirus [5].

High impact information on glycoprotein

• We have previously reported the purification of the prototypic es transporter from human erythrocytes and have shown that this glycoprotein of apparent M, 55,000 is immunologically related to nucleoside transporters from several other species and tissues, including human placenta [6].
• Wnt proteins are secreted, cysteine-rich glycoprotein ligands with numerous roles during animal development [7].
• The soluble, 170 kDa glycoprotein occurs throughout Drosophila embryos, in microsomes of highly secretory Drosophila Kc cells and in small amounts in cell culture media [8].
• Identification of the major soluble cuticular glycoprotein of lymphatic filarial nematode parasites (gp29) as a secretory homolog of glutathione peroxidase [9].
• An extracellular matrix-associated glycoprotein expressed in a variety of tissues during embryogenesis and repair, SPARC contains modular domains that can function independently to bind cells and matrix components [10].

Biological context of glycoprotein

• We have previously demonstrated that one such molecule, the phosphorylcholine-containing glycoprotein ES-62, acts to bias the immune response toward an anti-inflammatory/Th2 phenotype that is conducive to both worm survival and host health [11].
• In this review we discuss the immunomodulatory effects of the phosphorylcholine-containing filarial nematode-secreted glycoprotein ES-62 and describe the intracellular signal transduction pathways it targets to achieve these effects [12].
• Previous studies have shown that the secreted phosphorylcholine-containing glycoprotein of filarial nematodes, ES-62, is only present in the post-infective life-cycle stages, but that the mRNA is transcribed throughout the worm's life-cycle [13].
• Linked to parasite-specific glycoprotein glycans or glycolipids, it is assumed to be responsible for a variety of immunological effects, including invasion mechanisms and long-term persistence of parasites within the host [14].
• These findings have prompted the hypothesis that there could be additional glycoprotein hormones in vertebrate genomes [15].

Anatomical context of glycoprotein

• Here we demonstrate that ES-62, a phosphorylcholine-containing glycoprotein released by the rodent filarial parasite Acanthocheilonema viteae, interferes with activation of B lymphocytes by differential modulation of protein kinase C isoform expression [16].
• In this review, we will discuss the immunomodulatory effects of the phosphorylcholine-containing filarial nematode glycoprotein, ES-62, on the host immune system and summarise the results of our studies to identify the intracellular signalling pathways targeted by ES-62 to achieve these effects [17].
• To date the molecular mechanisms underlying this ability have not been defined but we now demonstrate that ES-62, a phosphorylcholine (PC)-containing glycoprotein released by the rodent filarial parasite Acanthocheilonema viteae, is able to render Jurkat T cells anergic to intracellular signalling via the antigen receptor (TCR) [18].
• In vivo exposure of murine dendritic cell and macrophage bone marrow progenitors to the phosphorylcholine-containing filarial nematode glycoprotein ES-62 polarizes their differentiation to an anti-inflammatory phenotype [19].
• Inhibitory effects of human neutrophil functions by the 45-kD glycoprotein derived from the parasitic nematode Trichinella spiralis [20].

Associations of glycoprotein with chemical compounds

• ES-62 is a phosphorylcholine-containing glycoprotein secreted by filarial nematodes, which has previously been shown to possess a range of immunomodulatory capabilities [21].
• The authentic eggshell protein has been identified as a glycoprotein with a molecular weight of about 10000, as determined by dodecylsulphate/polyacrylamide gel electrophoresis [22].
• Parenteral vaccination, using a 40-mer synthetic peptide from a 43,000 MW immunodominant glycoprotein secreted by the intestinal nematode parasite Trichinella spiralis, induced high levels of protection against a subsequent challenge infection in mice [23].
• By (i) measuring transfer of radio-isotope labelled PC from CDP-choline to parasite molecules and (ii) employing inhibitors of CDP-choline synthesis, we have investigated whether CDP-choline can act as a source of PC for transfer to ES-62, a major secreted glycoprotein of the rodent filarial nematode Acanthocheilonema viteae [24].
• The expressed protein binds a glycoprotein of 120 kDa from pig tongue epithelium on Western blots, and this is also inhibited by lactose [25].

Physical interactions of glycoprotein

• In mammals, the dystrophin-glycoprotein complex (DGC) includes dystrophin, as well as transmembrane and cytoplasmic proteins [26].

Other interactions of glycoprotein

• Molecular cloning and demonstration of an aminopeptidase activity in a filarial nematode glycoprotein [27].
• Chemical degradation of one particular epitope recognized by monoclonal antibody PP1/117, and designated ep117, occurred after treatment with NaOH, periodate or Proteinase K, suggesting that an O-linked glycoprotein may be involved [28].
• A glycoprotein analogous to viral fusion proteins has been identified on the surface of guinea pig sperm (PH-30/fertilin) and is implicated in sperm-egg fusion. adm-1 is the first reported invertebrate gene related to PH-30 and a family of proteins containing snake venom disintegrin- and metalloprotease-like domains [29].
• This article is an attempt to provide, in an easily accessible format, a compilation of genes and cDNAs that have been sequenced and deposited in GenBank that encode transferase enzymes involved in eukaryotic glycoprotein or glycolipid biosynthesis [30].
• Western- and lectin-blotting of the shed coat material demonstrated 2 prominent entities; a 90 kDa glycoprotein, which bound Datura stramonium agglutinin and was resistant to N- and O-glycanase treatment and a 47-60 kDa set of protein(s) [31].

Analytical, diagnostic and therapeutic context of glycoprotein

• The T. spiralis beta-N-acetyl-D-hexosaminidase is a glycoprotein based on its binding to lentil-lectin Sepharose affinity column and its specific binding of concanavalin A on Western blots [32].
• ES-62 is a PC-containing glycoprotein, which is secreted by the rodent filarial nematode Acanthocheilonema viteae and which provides a model system for the dissection of the mechanisms of immune evasion induced by related PC-containing glycoproteins expressed by human filarial nematodes [33].
• Sequence alignments showed that the TM region of the nematode receptor has 30% identity and 50% similarity to the same region in mammalian glycoprotein hormone receptors [34].
• Using pairwise sequence analysis of the complete human genome, we have identified two novel glycoprotein hormone subunit-related genes [35].

References