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991.
992.
Hepatitis B virus (HBV)-specific cytotoxic T-cell (CTL) response in humans: characterization of HLA class II-restricted CTLs that recognize endogenously synthesized HBV envelope antigens.
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A Penna P Fowler A Bertoletti S Guilhot B Moss R F Margolskee A Cavalli A Valli F Fiaccadori F V Chisari 《Journal of virology》1992,66(2):1193-1198
In this study, we show that CD4+, hepatitis B virus (HBV) envelope-specific T-cell clones produced by stimulation with a particulate antigen preparation are able to recognize and kill not only autologous antigen-presenting cells incubated with exogenous HBV envelope antigens but also autologous HLA class II-positive cells expressing endogenously synthesized HBV envelope antigens following infection with recombinant vaccinia viruses or transfection with recombinant Epstein-Barr virus expression vectors. Experiments with lysosomotropic agents and brefeldin A suggest that the endosomal compartment is likely involved in the processing of endogenously synthesized viral proteins for recognition by CD4+ T cells. Our study indicates that HBV envelope-specific, HLA class II-restricted CD4+ cytotoxic T lymphocytes can potentially participate in the immune clearance of HBV-infected cells and the pathogenesis of hepatocellular injury in hepatitis B. 相似文献
993.
994.
The vaccinia virus K3L gene product potentiates translation by inhibiting double-stranded-RNA-activated protein kinase and phosphorylation of the alpha subunit of eukaryotic initiation factor 2. 总被引:19,自引:7,他引:12
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Interferon resistance of vaccinia virus is mediated by specific inhibition of phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha) by the double-stranded-RNA-activated (DAI) protein kinase. Vaccinia virus encodes a homolog of eIF-2 alpha, K3L, the deletion of which renders the virus sensitive to interferon treatment. We have studied the mechanism by which this protein product elicits interferon resistance in a transient DNA transfection system designed to evaluate regulators of eIF-2 alpha phosphorylation. In this system, translation of a reporter gene mRNA is inefficient because of eIF-2 phosphorylation mediated by the DAI protein kinase. Cotransfection of the K3L gene enhances translation of the reporter mRNA in this system. The K3L protein inhibits eIF-2 alpha phosphorylation and DAI kinase activation, apparently without being phosphorylated itself. Inhibition of protein synthesis, elicited by expression of a mutant Ser-51----Asp eIF-2 alpha designed to mimic a phosphorylated serine, is not relieved by the presence of K3L, suggesting that K3L cannot bypass a block imposed by eIF-2 alpha phosphorylation. The results suggest that K3L acts as a decoy of eIF-2 alpha to inhibit DAI kinase autophosphorylation and activation. Another vaccinia virus gene product, K1L, which is required for growth of vaccinia virus on human cells, does not enhance translation in this assay. 相似文献
995.
Phosphorylation of ligand-gated ion channels: a possible mode of synaptic plasticity. 总被引:15,自引:0,他引:15
Most neurotransmitter receptors examined to date have been shown either to be regulated by protein phosphorylation or to contain consensus sequences for phosphorylation by protein kinases. Neurotransmitter receptors that mediate rapid synaptic transmission in the nervous system are the ligand-gated ion channels and include the nicotinic acetylcholine receptors of muscle and nerve and the excitatory and inhibitory amino acid receptors: the glutamate, GABAA, and glycine receptors. These receptors are multimeric proteins composed of homologous subunits which each span the membrane several times and contain a large intracellular loop that is a mosaic of consensus sites for protein phosphorylation. Recent evidence has suggested that extracellular signals released from the presynaptic neuron, such as neurotransmitters and neuropeptides as well as an extracellular matrix protein, regulate the phosphorylation of ligand-gated ion channels. The functional effects of phosphorylation are varied and include the regulation of receptor desensitization rate, subunit assembly, and receptor aggregation at the synapse. These results suggest that phosphorylation of neurotransmitter receptors represents a major mechanism in the regulation of their function and may play an important role in synaptic plasticity. 相似文献
996.
Mechanism of cholera toxin activation by a guanine nucleotide-dependent 19 kDa protein 总被引:7,自引:0,他引:7
Cholera toxin causes the devastating diarrheal syndrome characteristic of cholera by catalyzing the ADP-ribosylation of Gs alpha, a GTP-binding regulatory protein, resulting in activation of adenylyl cyclase. ADP-ribosylation of Gs alpha is enhanced by 19 kDa guanine nucleotide-binding proteins known as ADP-ribosylation factors or ARFs. We investigated the effects of agents known to alter toxin-catalyzed activation of adenylyl cyclase on the stimulation of toxin- and toxin subunit-catalyzed ADP-ribosylation of Gs alpha and other substrates by an ADP-ribosylation factor purified from a soluble fraction of bovine brain (sARF II). In the presence of GTP, sARF II enhanced activity of both the toxin catalytic unit and a reduced and alkylated fragment ('A1'), as a result of an increase in substrate affinity with no significant effects on Vmax. Activation of toxin was independent of Gs alpha and was stimulated 4-fold by sodium dodecyl sulfate, but abolished by Triton X-100. sARF II therefore serves as a direct allosteric activator of the A1 protein and may thus amplify the pathological effects of cholera toxin. 相似文献
997.
Specific sequence elements are required for the expression of functional tumor necrosis factor-alpha-converting enzyme (TACE). 总被引:4,自引:0,他引:4
M E Milla M A Leesnitzer M L Moss W C Clay H L Carter A B Miller J L Su M H Lambert D H Willard D M Sheeley T A Kost W Burkhart M Moyer R K Blackburn G L Pahel J L Mitchell C R Hoffman J D Becherer 《The Journal of biological chemistry》1999,274(43):30563-30570
The tumor necrosis factor-alpha-converting enzyme (TACE) is a membrane-anchored zinc metalloprotease involved in precursor tumor necrosis factor-alpha secretion. We designed a series of constructs containing full-length human TACE and several truncate forms for overexpression in insect cells. Here, we demonstrate that full-length TACE is expressed in insect cells inefficiently: only minor amounts of this enzyme are converted from an inactive precursor to the mature, functional form. Removal of the cytoplasmic and transmembrane domains resulted in the efficient secretion of mature, active TACE. Further removal of the cysteine-rich domain located between the catalytic and transmembrane domains resulted in the secretion of mature catalytic domain in association with the precursor (pro) domain. This complex was inactive and function was only restored after dissociation of the complex by dilution or treatment with 4-aminophenylmercuric acetate. Therefore, the pro domain of TACE is an inhibitor of the catalytic domain, and the cysteine-rich domain appears to play a role in the release of the pro domain. Insect cells failed to secrete a deletion mutant encoding the catalytic domain but lacking the inhibitory pro domain. This truncate was inactive and extensively degraded intracellularly, suggesting that the pro domain is required for the secretion of functional TACE. 相似文献
998.
X-Linked Agammaglobulinemia Patients Are Not Infected with Epstein-Barr Virus: Implications for the Biology of the Virus 总被引:5,自引:2,他引:3
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Glenda C. Faulkner Scott R. Burrows Rajiv Khanna Denis J. Moss A. Graham Bird Dorothy H. Crawford 《Journal of virology》1999,73(2):1555-1564
Epstein-Barr virus (EBV) infects both B lymphocytes and squamous epithelial cells in vitro, but the cell type(s) required to establish primary and persistent infection in vivo has not been definitively elucidated. The aim of this study was to investigate a group of individuals who lack mature B lymphocytes due to the rare heritable disorder X-linked agammaglobulinemia in order to determine the role of the B cell in the infection process. The results show that none of these individuals harbored EBV in their blood or throat washings. Furthermore, no EBV-specific memory cytotoxic T lymphocytes were found, suggesting that they had not undergone infection in the past. In contrast, 50% of individuals were found to carry human herpesvirus 6, showing that they are infectible by another lymphotropic herpesvirus. These results add weight to the theory that B lymphocytes, and not oropharyngeal epithelial cells, may be required for primary infection with EBV. 相似文献
999.
S B Moss R M Turner K L Burkert H VanScoy Butt G L Gerton 《Biology of reproduction》1999,61(2):335-342
Protein kinase A regulates sperm motility through the cAMP-dependent phosphorylation of proteins. One mechanism to direct the activity of the kinase is to localize it near its protein substrates through the use of anchoring proteins. A-Kinase anchoring proteins (AKAPs) act by binding the type II regulatory subunit of protein kinase A and tethering it to a cellular organelle or cytoskeletal element. We showed previously that mAKAP82, the major protein of the fibrous sheath of the mouse sperm flagellum, is an AKAP. The available evidence indicates that protein kinase A is compartmentalized to the fibrous sheath by binding mAKAP82. To characterize AKAP82 in bovine sperm, a testicular cDNA library was constructed and used to isolate a clone encoding bAKAP82, the bovine homologue. Sequence analysis showed that the primary structure of bAKAP82 was highly conserved. In particular, the amino acid sequence corresponding to the region of mAKAP82 responsible for binding the regulatory subunit of protein kinase A was identical in the bull. Bovine AKAP82 was present in both epididymal and ejaculated sperm and was localized to the entire principal piece of the flagellum, the region in which the fibrous sheath is located. Finally, bAKAP82 bound the regulatory subunit of protein kinase A. These data support the idea that bAKAP82 functions as an anchoring protein for the subcellular localization of protein kinase A in the flagellum. 相似文献
1000.