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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelin oligodendrocyte glycoprotein, (MOG), a quantitatively minor central nervous system (CNS) myelin component, is a candidate target antigen for autoimmune-mediated demyelination. It is a highly hydrophobic protein present in very small amounts in CNS tissue and thereby difficult to purify. Our aim was to devise a purification procedure that would yield sufficient quantities of highly purified MOG to subsequently test its potential encephalitogenic activity, as well as investigate the humoral and cell-mediated responses to this antigen in naturally occurring and experimentally induced autoimmune demyelinating diseases. MOG was purified from human CNS white matter using immunoaffinity chromatography, a procedure that gave a final yield of MOG corresponding to 0.02% total white matter protein. The final product, which migrated as two bands of molecular weight 28 kDa and 58 kDa, was highly pure as shown also by specific reactivity with monoclonal anti-MOG antibodies on immunoblots in the absence of any detectable reactivity with antibodies specific for myelin basic protein, proteolipid protein and myelin-associated glycoprotein. Partial amino acid sequence was obtained from both MOG bands separated by SDS-PAGE and electroblotted onto PVDF. The sequence of the first 17 N-terminal amino acids had approximately 55% homology with the reported rat MOG sequence deduced from the cloned cDNA sequence; small internal sequences obtained showed also very high homology. Our purified MOG preparations have been used to investigate T cell response to MOG by peripheral blood lymphocytes of multiple sclerosis patients and to induce a relapsing remitting demyelinating disease in Lewis rats.
Biochem Mol Biol Int 1993 Aug
PMID:Preparation of highly purified human myelin oligodendrocyte glycoprotein in quantities sufficient for encephalitogenicity and immunogenicity studies. 822 Feb 43

Raf-1 is a serine/threonine kinase which is essential in cell growth and differentiation. Tyrosine kinase oncogenes and receptors and p21ras can activate Raf-1, and recent studies have suggested that Raf-1 functions upstream of MEK (MAP/ERK kinase), which phosphorylates and activates ERK. To determine whether or not Raf-1 directly activates MEK, we developed an in vitro assay with purified recombinant proteins. Epitope-tagged versions of Raf-1 and MEK and kinase-inactive mutants of each protein were expressed in Sf9 cells, and ERK1 was purified as a glutathione S-transferase fusion protein from bacteria. Raf-1 purified from Sf9 cells which had been coinfected with v-src or v-ras was able to phosphorylate kinase-active and kinase-inactive MEK. A kinase-inactive version of Raf-1 purified from cells that had been coinfected with v-src or v-ras was not able to phosphorylate MEK. Raf-1 phosphorylation of MEK activated it, as judged by its ability to stimulate the phosphorylation of myelin basic protein by glutathione S-transferase-ERK1. We conclude that MEK is a direct substrate of Raf-1 and that the activation of MEK by Raf-1 is due to phosphorylation by Raf-1, which is sufficient for MEK activation. We also tested the ability of protein kinase C to activate Raf-1 and found that, although protein kinase C phosphorylation of Raf-1 was able to stimulate its autokinase activity, it did not stimulate its ability to phosphorylate MEK.
Mol Cell Biol 1993 Nov
PMID:Reconstitution of the Raf-1-MEK-ERK signal transduction pathway in vitro. 841 57

The fission yeast dsk1+ gene, a multicopy suppressor for cold-sensitive dis1 mutants, encodes a novel 61-kd protein kinase. It is a phosphoprotein, and phosphoserine is the major phosphorylated amino acid. Hyperphosphorylation of dsk1 causes a mobility shift, resulting in two dsk1-specific protein bands. The phosphorylation pattern is strikingly altered when cell cycle progression is delayed or arrested. The slowly migrating phosphorylated form is prominent in mitotically arrested cells, and the fast migrating form is enriched in interphase-arrested cells. dsk1 is a protein kinase. It auto-phosphorylates as well as phosphorylates myelin basic protein (MBP). Phosphotyrosine as well as phosphoserine/threonine were found in autophosphorylation, but no tyrosine phosphorylation occurs when MBP was used as the substrate. The dsk1 immunoprecipitates from mitotically arrested cells have a several-fold higher kinase activity than that from wild type. The haploid gene disruptant is viable, indicating that the dsk1+ gene is non-essential for viability. High dosage of dsk1+, however, strongly delays the G2/M progression. Immunofluorescence microscopy using anti-dsk1 antibody shows that localization pattern of dsk1 protein strikingly alters depending on cell cycle stages. In G2-arrested cells, dsk1 locates in the cytoplasm, whereas in mitotically arrested cells, nuclear stain is intense. In wild-type cells, nuclear stain is seen only in mitotic cells. Hence dsk1 protein may play an important role in mitotic control by altering cellular location, degree of phosphorylation and kinase activity. We discuss possible roles of dsk1 kinase as an add-on regulator in mitosis.
Mol Biol Cell 1993 Mar
PMID:A mitotic role for a novel fission yeast protein kinase dsk1 with cell cycle stage dependent phosphorylation and localization. 848 17

We have designed and expressed in bacteria a recombinant fetal form of human myelin basic protein (21.5 kDa isoform; rhMBP21.5), a candidate autoantigen in multiple sclerosis. An exon 2 insertion, carboxy-terminal histidine tag and preferred bacterial codons differentiate the MBP21.5 gene from that encoding the adult, brain-derived form of human MBP (18.5 kDa isoform; hMBP18.5). MBPs were expressed at high levels in E. coli and extracted from whole cells by simultaneous acid solubilization and mechanical disruption. A nearly two-fold increase in recombinant protein was detected in strains harboring MBP genes with bacterial preferred codons compared to genes containing human codons. The recombinant molecules were purified in two steps, first by reversed-phase chromatographic separation and then by metal affinity chromatography. Dimeric forms of recombinant MBP21.5 were detected under physiological conditions, however, substitution of a serine for the single cysteine at amino acid residue 81 resulted in only monomer formation. All forms of recombinant MBPs induced proliferative responses of human T lymphocytes specific for epitopes in MBP18.5 kDa. In contrast, human T cell lines that recognize an exon 2-encoded epitope of MBP responded to the 21.5 kDa isoform of MBP, but not the 18.5 kDa isoform.
Mol Immunol 1995 Oct
PMID:Purification of immunologically active recombinant 21.5 kDa isoform of human myelin basic protein. 854 62

The cell-surface glycoprotein, CD9, has been implicated in hematopoietic and Schwann cell signaling in vitro. In vivo, Schwann cell CD9 expression follows a developmental time course that parallels that of myelin genes. Here we report that Schwann cell CD9 mRNA expression is regulated by axonal contact in culture and in vivo. Following adult rat sciatic nerve injury, CD9 mRNA expression in distal nerve sections is correlated with the presence of axons; CD9 is down-regulated when axons are degenerating and is reexpressed when axons are regenerating, but not if they are prevented from doing so by transection. CD9 regulation in cultured Schwann cells is also dependent on the presence of neurons such that dissociated Schwann cells down-regulate CD9 mRNA expression in culture, but in the presence of sensory neurons they continue to express CD9. Therefore, regulation of Schwann cell CD9 expression parallels that of myelin genes protein 0 and myelin basic protein in culture and in vivo. A signaling role for CD9 in nerve development and regeneration is proposed.
Mol Cell Neurosci 1995 Oct
PMID:Schwann cell CD9 expression is regulated by axons. 858 16

We report the X-ray scattering study of sciatic and optic nerve myelin from shiverer, jimpy and quaking mice mutants and from the corresponding controls. These three mutations are known to affect dramatically central nervous system (CNS) myelin and to induce comparatively minor alterations in peripheral nervous system (PNS) myelin. Scattering experiments and data reduction were carried out using the techniques and algorithms developed in our laboratory and previously applied to several problems involving the structure of myelin. In sciatic nerve the fraction of myelin elementary pairs of membranes (total myelin) decreases in shiverer and quaking nerves (by approximately 30%) but not in jimpy nerves; in all three mutants the fraction of myelin membrane pairs that are not regularly stacked in the sheaths (loose myelin), the average number of membranes per sheath and the packing disorder are the same as in the control nerves; the repeat distance D and the membrane distance Dcyt across the cytoplasmic space increase in shiverer and decrease in jimpy; in quaking, D also decreases and the decrease is smaller than in jimpy and is not specific for Dcyt; small changes are also observed in the electron density profiles. As for the optic nerve the myelin content decreases dramatically in the three mutants; the very weak signal attests to a tiny amount of pairs of membranes structurally similar to normal CNS myelin. It is surprising that the structure of CNS myelin should be almost normal in the absence of the major structural components, namely myelin basic protein (MBP) for shiverer of proteolipid protein (PLP) for jimpy. The question arises whether the composition of the residual pairs of membranes, operationally identified as myelin in the X-ray scattering experiments, mirrors the composition determined by chemical means on the fraction of nerve tissue histologically identified as myelin, or whether in all circumstances it remains approximately the same.
J Mol Biol 1996 Feb 23
PMID:Order-disorder phenomena in myelinated nerve sheaths. VI. The effects of quaking, jimpy and shiverer mutations: an X-ray scattering study of mouse sciatic and optic nerves. 859 99

Chemically and immunologically, myelin basic protein (MBP) is very similar with the basic protein extracted from animal and human tumors. The results of this study demonstrated that splenocytes from C57BL/6 mice bearing B16 melanoma cells are sensitized to MBP, suggesting that this protein may share common antigenic determinants with antigens from B16 melanoma cells. The RNA preparations isolated from lymphoid tissues of normal or immunized guinea pigs with bovine MBP are referred to as N-RNA or MBP-RNA, respectively. It was also found that MBP-RNA is active in transferring MBP reactivity to normal splenocytes whereas N-RNA had no effect. To investigate whether this transfer to MBP immunoreactivity could result in a protective immunity, C57BL/6 mice transplanted with B16 melanoma received normal splenocytes treated with N-RNA or MBP-RNA. Two weeks after injection of B16-F10 cells, the mice were sacrificed and the tumor of each animal was removed and weighed. A significant inhibition of B16 melanoma growth was only achieved in C57BL/6 mice treated by splenocytes incubated with MBP-RNA which acts as an anti-tumor RNA. In this context, MBP could be considered as a tumor antigen.
Cell Mol Biol (Noisy-le-grand) 1996 Mar
PMID:Anti-tumor effect of splenocytes treated with RNA from animals immunized with bovine myelin basic protein. 869 62

The secondary structure of myelin basic protein (MBP) in reconstituted central nervous system myelin was studied using Fourier transform infrared (FTIR) spectroscopy. The spectra of the protein in aqueous solution and in the lipid environment were compared and notable differences were observed. It is proposed that there are significant differences in the conformation of the protein in the contrasting environments. Significant increases in both alpha-helical structure and beta-structure were observed on reconstitution in myelin. The findings of this study also support the view that the presence of both alpha-helices and beta-structure plays a important role in membrane proteins.
Biochem Mol Biol Int 1996 Apr
PMID:A Fourier transform infrared spectroscopic study of the secondary structure of myelin basic protein in reconstituted myelin. 872 14

Circumstantial and experimental evidence has implicated the immune cytokine interferon-gamma (IFN-gamma) as a key mediator in the pathological changes that are observed in many demyelinating disorders, including the most common human demyelinating disease, multiple sclerosis. To produce an animal model with which to study the effects of IFN-gamma on the CNS, we have generated transgenic mice in which the expression of IFN-gamma has been placed under the transcriptional control of the myelin basic protein (MBP) gene. Transgenic mice generated with this construct have a shaking/shivering phenotype that is similar to that observed in naturally occurring mouse models of hypomyelination (e.g., shiverer, jimpy, quaking), and these transgenic animals have dramatically less CNS myelin than control animals. Reactive gliosis and increased macrophage/microglial F4/80 immunostaining were also observed. Additionally, major histocompatibility complex (MHC) class I and class II mRNA levels were increased in the CNS of MBP/IFN-gamma transgenic mice, and the increase in MHC class I mRNA expression was detected in both white and gray matter regions. Furthermore, cerebellar granule cell migration was abnormal in these animals. These results strongly support the hypothesis that IFN-gamma is a key effector molecule in immune-mediated demyelinating disorders and indicate that the presence of this cytokine in the CNS may also disrupt the developing nervous system.
Mol Cell Neurosci 1996 May
PMID:Targeted CNS expression of interferon-gamma in transgenic mice leads to hypomyelination, reactive gliosis, and abnormal cerebellar development. 881 62

Two forms of protein tyrosine phosphatases were partially purified from the musculo-cutaneous layer of Ascaris suum. A 50-55-kDa soluble form of the phosphatase cross-reacted with antisera raised against human PTP-1B and TC-PTP. Like the enzyme of human origin the phosphatase from Ascaris exhibited a preference for anionic substrates (tyrosine-phosphorylated carboxymethylated and maleylated lysozyme) and was inhibited by micromolar concentrations of vanadate, molybdate, Zn2+, heparin, and poly(Glu4Tyr). As revealed by immuno-cytochemistry, the phosphatase was mainly localized and appeared equally distributed in the cytoplasm, apart from the myofibrils, possibly in loose association with cytoskeletal elements. A second tyrosine phosphatase of 180 kDa molecular mass was mainly found in detergent extracts from a microsomal fraction. It showed no cross-reactivity with antisera raised against soluble mammalian phosphatases and dephosphorylated a basic substrate (Tyr-phosphorylated myelin basic protein). It was resistant to common inhibitors of mammalian tyrosine phosphatases except Zn2+ and thiol reagents.
Mol Biochem Parasitol 1996 May
PMID:Protein phosphotyrosine phosphatases in Ascaris suum muscle. 881 64


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