Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among the cytokines tested here (IL-2, IL-3, IL-4, IL-5, IL-6, granulocyte colony stimulating factor (G-CSF), granulocyte/macrophage colony stimulating factor (GM-CSF), interferon-alpha (IFN-alpha), interferon-beta (IFN-beta) and interferon-gamma (IFN-gamma] only interleukin 1(IL-1) augmented HIV-long terminal repeat(LTR) directed chloramphenicol acetyl transferase(CAT) activity in protein kinase C(PKC)-independent manner. However, a stimulation by IL-1 was not as efficient as that due to tumor necrosis factor and the HIV production was not significant. IL-1 was not cytotoxic to MOLT-4/HIV cells.
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PMID:Effect of interleukin-1 on the augmentation of human immunodeficiency virus gene expression. 248 Jul 82

We previously reported that the coculture of cloned, allospecific human T helper (Th) cells with allogenic B cells bearing the relevant major histocompatibility complex class II antigen induces expression of the B cell activation antigen CD23 (BLAST-2) on a fraction of the B cells. To determine if Th cell-induced CD23 expression defines a distinct subset of human B cells, allospecific Th cells were cultured with B cell fractions isolated on discontinuous Percoll gradients. Our results show that the majority of high density resting B cells, those bearing surface IgD and little of the 4F2 activation antigen, express high intensity CD23 after culture with relevant allospecific Th cells. Essentially all of the low density, presumably in vivo-activated, B cell subpopulation and a fraction of the high density B cell pool remain CD23 negative after repeated culture with relevant allospecific Th cells. We utilized the CD23 induction assay to investigate a potential synergistic effect in B cell activation mediated by Th cell signaling and antigen analog-induced cross-linking of B cell surface Ig receptors. These studies show that phorbols known to result in PKC activation, one of the biochemical consequences of sIg-mediated B cell signaling, enhance both the intensity of CD23 expression and the percentage of cells expressing CD23 after allospecific Th cell or IL-4 interaction with high density, but not low density B cells. Finally, we show that while Th-induced B cell activation, as measured by CD23 expression, is a property of high density B cells, induction of Th cell proliferation is a property of the low density B cell population. These results suggest that the antigen-specific interaction between Th cells and resting B cells may serve to activate the B cell in preference to the T cell.
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PMID:T helper cell-induced CD23 (BLAST-2) expression: an activation marker for the high density fraction of human B cells. 252 58

Membranes were isolated from B cells stimulated with phorbol 12-myristate 13-acetate (PMA) for a time sufficient to allow maximal redistribution and activation of protein kinase C (PKC). Exposure of such membranes to a short incubation with [gamma-32P]ATP resulted in the detection of at least nine unique or hyperphosphorylated membrane proteins by SDS-PAGE and autoradiography. The appearance of these phosphoproteins was blocked by pretreatment of the membranes with H-7 or sangivamycin, two selective inhibitors of PKC. In addition, membranes purified from B cells treated with an inactive phorbol ester or stimulated with dibutyryl cAMP failed to exhibit a pattern of new phosphoproteins. These results are consistent with the involvement of PKC in the phosphorylation of the proteins. These phosphoproteins are also candidates for proteins whose functions are modified as a consequence of early signal delivery to resting B cells following membrane immunoglobulin occupancy. This system was utilized to identify the heavy chain of MHC class I molecules as one of the membrane proteins phosphorylated by PKC. The MHC class II molecules were not phosphorylated in membranes isolated from PMA-treated normal B cells or from PMA-treated B cells which had previously been exposed to IL-4. These results indicate that class I, but not class II, MHC molecules are phosphorylated by PKC. It is possible that such a modification of cell surface class I molecules may be involved during the process of signal transduction leading to B cell activation.
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PMID:Phosphorylation of class I but not class II MHC molecules by membrane-localized protein kinase C. 263 45

The data presented here indicated that both membrane Ig and IL-4 receptors transduce signals across the plasma membrane of quiescent B cells, which results in the induction of c-fos and c-myc proto-oncogene mRNA expression. Monoclonal anti-Ig antibodies with specificity for mu, delta, or kappa chains, regardless of mitogenicity, induced increased c-fos and c-myc mRNA expression with kinetics and magnitude similar to that observed following stimulation of B cells with IL-4. Maximal levels of c-fos mRNA, approximately 30-fold over background, were observed 30 min after stimulation. Maximal levels of c-myc mRNA, approximately 10-fold over background, were observed 60 min after stimulation. Phorbol myristate acetate alone induced expression of these two oncogenes in a similar fashion, suggesting that protein kinase C may be involved in the regulation of their expression following anti-Ig crosslinking. Ionomycin induced only a small increase in c-myc and c-fos message (three- to four-fold), and did not synergize with phorbol myristate acetate, suggesting that the membrane Ig-mediated calcium mobilization may not play a major role in regulation of c-myc or c-fos expression in mouse B cells. In vitro nuclear run-on analyses indicate that c-myc expression is primarily regulated post-transcriptionally, whereas c-fos expression is regulated at the level of transcription. Anti-sense transcription was found to be constitutive for both the c-myc and C-fos loci and was further induced by anti-Ig and IL-4, suggesting an additional mechanism for regulation of these genes. The observation that both anti-Ig and IL-4 regulate the expression of c-fos and c-myc suggests that multiple second messenger generating systems regulate the expression of these oncogenes in normal B cells and that their expression may be necessary, but is not sufficient to drive quiescent B cells into cell cycle.
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PMID:Induction of c-fos and c-myc expression during B cell activation by IL-4 and immunoglobulin binding ligands. 278 45

The findings presented in this study provide evidence that BSF1 receptors and mIg transmit signals via dissimilar transduction mechanisms that result in a common biologic response, hyper-Ia expression. Specifically, BSF1-containing supernatant does not induce PtdInsP2 hydrolysis as determined by measurement of PtdOH and InsP3. Additionally, BSF1 does not stimulate Ca2+ mobilization, PKC translocation from cytosol to membrane, or membrane depolarization. All of these metabolic events appear to play a central role in hyper-Ia expression mediated by mIg and are initiated after treatment of resting B cells with anti-Ig antibodies. In vitro phosphorylation studies with partially purified plasma membranes from resting B cells revealed that BSF1 interaction with membrane receptors stimulates a membrane-associated protein kinase that phosphorylates an endogenous protein of 44 KDa. Anti-Ig does not stimulate phosphorylation of the 44 KDa protein, suggesting that it does not activate the membrane-associated protein kinase. This observation provides the first evidence of a signal transduction mechanism associated with BSF1-receptor ligation. It indicates that although BSF1 does not modulate events associated with PKC activation, it may function via activation of a membrane-associated protein kinase. This provides a focal point for further studies directed at elucidating signal transduction resulting from BSF1-receptor interaction.
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PMID:BSF1 induces membrane protein phosphorylation but not phosphoinositide metabolism, Ca2+ mobilization, protein kinase C translocation, or membrane depolarization in resting murine B lymphocytes. 302 86

A B cell-specific monoclonal antibody (anti-Ba) was prepared. In two-color FACS analysis the anti-Ba reacted with a subpopulation of Ig+ or B1+ cells obtained from tonsils, but did not react with most B1+ cells derived from PBL. Activation of B cells from PBL with TPA or anti-mu induced Ba expression and the addition of PHA-conditioned supernatant with anti-mu-enhanced Ba expression. Other B cell activators, such as Staphylococcus aureus Cowan I (Staph-A) or PWM plus T cells, could induce Ba expression. Ba expression was observed 6 hr after stimulation and reached a peak level at 72 hr. Ba expression was strictly restricted to B cells. H-7, a specific inhibitor of protein kinase C (C-kinase), displayed a dose-dependent inhibitory effect on Ba expression, showing dependency on C-kinase for Ba expression. Anti-Ba inhibited B cell proliferation induced by anti-mu and B-BCGF distinct from BSF-1. The results presented in this study suggest that the Ba antigen on B cells may be comparable to the Tac antigen on T cells.
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PMID:Expression and function of an early activation marker restricted to human B cells. 308 51

We have analyzed the mechanism of action of BSF-1 on class II gene expression in two murine pre-B cell lines that are at different stages of differentiation. In vitro transcription assays demonstrated that BSF-1 induced rapid transcription of class II genes within 1 hr by a mechanism that was independent of protein synthesis. Although cell surface expression of class II was detectable by 2 hr after induction and persisted for up to 96 hr after removal of BSF-1, levels of class II-specific mRNA and density of cell surface class II increased to a maximum between 24 and 72 hr after induction. Furthermore, prostaglandin E2 prevented the induction of class II gene expression by BSF-1. The effects of BSF-1 are unlikely to be mediated through calcium fluxes or activation of protein kinase C, since treatment with agents such as PMA and the calcium ionophore A23187 did not result in expression of class II molecules. Other lymphokines, such as IFN-gamma, IL 1, IL 2, and IL 3, did not affect class II gene expression in these two cell lines. These data provide further insight into the mechanisms by which class II gene expression is regulated in B cells.
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PMID:Regulation of class II gene expression: analysis in B cell stimulatory factor 1-inducible murine pre-B cell lines. 309 28

Murine macrophages express high levels of nitric oxide synthase and produce large amounts of nitric oxide (NO) when stimulated with certain cytokines in the presence of a trace amount of lipopolysaccharide (LPS). The stimulatory cytokines include interleukin-1 (IL-1), interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and migration inhibitory factor. Activated macrophages are highly effective killers of intra- and extra-cellular pathogens. However, as excessive NO can lead to immunopathology (diabetes, graft-v.-host disease, EAE, liver cirrhosis, rheumatoid arthritis), NO production is necessarily under tight regulation. A number of cytokines, including IL-4, IL-10 and transforming growth factor-beta, can down regulate the induction of NO synthase in macrophages. In addition, macrophages exposed to LPS alone and then stimulated with a mix of IFN-gamma and LPS express significantly lower levels of NO synthase than cells stimulated without pre-exposure to LPS. Furthermore, NO can reduce the activity of NO synthase by feedback inhibition, and also inhibit the production of IFN-gamma by Th1 cells (thus turning off its own synthesis from upstream). The regulatory pathways involve tyrosine kinase and protein kinase C.
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PMID:The role of nitric oxide in parasitic diseases. 751 Jan

We developed and applied a quantitative competitive polymerase chain reaction method to study the expression of various cytokine genes in Con A-stimulated murine splenocytes. This method relies on the use of competitive templates that differ from the target cytokine cDNA templates only by the introduction of a unique restriction endonuclease site in the center of each competitive template. After same-tube amplification using a single pair of oligonucleotide primers for both the target and competitive templates, restriction with the unique endonuclease yields 2 species that are readily resolved on agarose gel electrophoresis: full-length target and half-length competitor fragments. Using this method, we studied the time course and effects of CsA and rapamycin on IL-2, IFN-gamma, IL-4, and IL-10 gene expression following Con A stimulation. IL-2, IFN-gamma, and IL-10 share a common pattern of gene expression peaking at approximately 6 hr, while IL-4 gene expression peaks later, at approximately 20 hr. CsA very effectively inhibits expression of IL-2, IFN-gamma, and IL-4, but it inhibits IL-10 expression only 65%. Rapamycin inhibits IL-10 gene expression 100% and is less effective inhibiting the other cytokines. This pattern of inhibition is consistent with a calcium and protein kinase C independent pathway for IL-10 gene regulation and supports the notion that CsA and rapamycin may be used together to advantage.
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PMID:Quantitative comparison of rapamycin and cyclosporine effects on cytokine gene expression studied by reverse transcriptase-competitive polymerase chain reaction. 751 20

IL-5 was produced in vitro by peripheral blood mononuclear cells (PBMC) of mite-sensitive atopic patients upon challenge with specific allergen, while PBMC of healthy controls produced essentially no IL-5. Stimuli delivered by the combination of phorbol ester and Ca2+ ionophore induced marked IL-5 production by PBMC obtained from atopic and non-atopic asthmatics, suggesting that both protein kinase C and Ca2+ influx are required for IL-5 production. CD2- or CD4-bearing cell depletion almost completely removed IL-5-producing cells while CD8-bearing cell depletion rather enriched them. These findings indicate that CD4+ T cells are the principal source of IL-5 in PBMC. The capacity of PBMC of atopic asthmatics, non-atopic asthmatics and healthy controls to produce IL-2, IL-4, IL-5 and IFN-gamma was compared, to find that cytokine-producing capacities other than that of IL-5 (IL-2, IL-4 and IFN-gamma) were not significantly different among the three groups. Dexamethasone, FK506 and cyclosporin A suppressed IL-5 production in vitro in a dose-dependent manner. Clear dose-dependent suppression of IL-5 gene expression by FK506 was also observed. Treatment of asthmatic patients with inhaled glucocorticoid (beclomethasone dipropionate) ameliorated clinical symptoms, improved lung function and markedly suppressed IL-5 production by PBMC, suggesting the essential role of IL-5 in the pathogenesis of bronchial asthma and the clinical importance of its regulation.
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PMID:IL-5 production by CD4+ T cells of asthmatic patients is suppressed by glucocorticoids and the immunosuppressants FK506 and cyclosporin A. 754 Aug 62


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