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)

This study was initiated to examine the role of cyclic nucleotides in the regulation of the expression of the Ly-6E cell surface Ag by IFN. As a model system, we used the YAC T cell lymphoma where this Ag is constitutively absent but is highly inducible by both IFN-gamma and IFN-alpha/beta. Treatment with cAMP or cGMP analogs did not cause Ly-6E expression in the absence of IFN. However, treatment with cAMP analogs, but not with cGMP analogs, markedly altered Ly-6E expression triggered by IFN, both at the mRNA and at the cell surface protein levels. Interestingly, these effects depended on whether Ly-6E induction was mediated by IFN-gamma or IFN-alpha/beta. Thus, the response to IFN-gamma was enhanced up to tenfold, whereas the response to IFN-alpha/beta was suppressed by 90-95%. Similar differential modulations of Ly-6E induction were also exerted by forskolin and cholera toxin, which are known to elevate intracellular cAMP concentration through distinct mechanisms. A YAC cell variant (C10) was isolated, where cAMP analogs or cAMP inducers could not modify Ly-6E induction. Although resistant to the biological effect of cAMP, the C10 mutant exhibited normal IFN-mediated Ly-6E responses. Moreover, in this mutant, Ly-6E induction was still affected by the PKC activator PMA, as in wild-type YAC cells. Altogether, our data demonstrate that cAMP (and cGMP) is not directly involved as second messenger in Ly-6E induction mediated by IFNs. However, a rise of cAMP modulates in an opposite fashion the Ly-6E-inducing actions of IFN-gamma and IFN-alpha/beta, which suggests that the two types of IFN utilize separate biochemical pathways to regulate Ly-6E expression.
 ...
PMID:Modulation of IFN-mediated Ly-6E antigen induction by cAMP in a T cell lymphoma: opposite effects on the responses to IFN-gamma and IFN-alpha/beta. 184 25

Human embryo fibroblasts (HEF) were primed when treated with a synthetic diacylglycerol, OAG, or the phorbol esters TPA or DBP. These primed HEF produce more interferon-beta (IFN-beta) in response to poly(rI).poly(rC), or poly(rA).poly(rU), added 1 h or 18 h later. These priming agents are activators of protein kinase C (PKC). A PKC inhibitor, H-7, blocked their priming effects and also those of human IFN-alpha. Two phorbol esters, 4PDD and 4P, that did not activate PKC did not prime HEF cells. Pretreatment of HEF cells for 1 h or 18 h with TPA or DBP reduced their susceptibility to infection with vesicular stomatitis virus (VSV); this effect was blocked by treatment with H-7. In contrast, the antiviral effects of IFN-alpha were not blocked by H-7, or by previous down-regulation of PKC by prolonged treatment of HEF cells with TPA. These results show that in HEF cells treated with IFN-alpha PKC plays a role in the processes that prime for IFN production, but not in those which establish the antiviral state.
 ...
PMID:The priming effect of human interferon-alpha is mediated by protein kinase C. 196 49

Interferon-alpha (IFN alpha) and platelet-derived growth factor (PDGF) each rapidly stimulate binding of nuclear factors from Balb/c 3T3 fibroblasts, to a 29-base pair regulatory sequence derived from the 5' upstream region of the murine 2-5A synthetase gene. This regulatory sequence contains a functional interferon-stimulated response element (ISRE) and also functions as a PDGF-responsive sequence. We show that IFN alpha induces binding of a protein of molecular mass 65 kDa to the ISRE. Constitutively expressed ISRE-binding proteins of 98 and 150 kDa are also demonstrated. Binding of inducible factors to the ISRE increases significantly within 15 min of IFN alpha or PDGF treatment. PDGF-induced binding is not mediated by IFN beta. The protein kinase inhibitors, staurosporine and K252a, block PDGF-induced ISRE binding and 2-5A synthetase gene expression. IFN alpha-induced ISRE binding and gene activation are not blocked by these inhibitors. Treatment of cells with 12-O-tetradecanoyl-13-acetate or dibutyryl cyclic AMP does not activate ISRE binding factors or 2-5A synthetase gene expression. PDGF responsiveness of the ISRE in vivo is also sensitive to staurosporine, indicating that inhibition of a protein kinase activity blocks the PDGF-specific transcriptional signal. Our data indicate the signal transduction pathway for IFN alpha-induced, ISRE-dependent transcription is distinct from the PDGF-induced ISRE response and is likely independent of cyclic AMP-dependent protein kinase and protein kinase C activities.
 ...
PMID:Induced factor binding to the interferon-stimulated response element. Interferon-alpha and platelet-derived growth factor utilize distinct signaling pathways. 202 93

Cyclosporine, but not its nonimmunosuppressive analog cyclosporine H (CsH), caused in a variety of hematopoietic cell types a growth arrest in the G0/G1 phase of the cell cycle. This arrest was associated with a significant reduction in the c-myc mRNA levels, which could be observed already 1 hr following CsA treatment. Similarity between the antiproliferative effects of CsA and IFN-alpha was observed. Thus, the IFN-alpha sensitive human B-lymphoblastoid cell line Daudi was also sensitive to CsA while an IFN-alpha resistant variant of Daudi cells was found to be resistant to CsA as well. Inhibition of protein synthesis with cycloheximide during IFN-alpha or CsA treatment blocked their ability to reduce the expression of c-myc. Depletion of protein kinase C (PKC) activity from cells by pretreatment of Daudi cells with phorbol.12-myristate 13-acetate (PMA) abolished the G0/G1 arrest induced by both CsA and IFN-alpha. Combinations of low concentrations of CsA and IFN-alpha had synergistic effects on cell-cycle distribution and on c-myc mRNA level, suggesting that CsA and IFN-alpha differ in some features of their antiproliferative action. This conclusion was supported by the observation that a CsA-resistant variant of Daudi cells was found to retain its sensitivity to IFN-alpha. In addition, reduction of ornithine decarboxylase mRNA expression was obtained with IFN-alpha but not with CsA. Taken together, our results suggest that CsA and IFN-alpha share some common element(s) in the pathways of their antiproliferative activity. The possible mechanisms of their antigrowth effects and the clinical significance of our findings are discussed.
 ...
PMID:The antiproliferative effect of cyclosporine on hematopoietic and lymphoblastoid cell lines--common mechanistic elements with interferon-alpha. 204

Human interferon-alpha (Hu-IFN alpha) and phorbol myristate acetate (PMA), a direct activator of protein kinase C (PK-C), induce the translocation of protein kinase C from the cytosol to the membrane fraction. By the use of transmission (TEM) and scanning (SEM) electron microscopy we have shown that treatment of human amniotic cells (UAC) with Hu-IFN alpha resulted in profound changes in the shape, volume and ultrastructure of the cells. Most treated cells had enlarged nuclei with marginal condensation of chromatin. Nucleolar segregation, disintegration and clumping of nucleolar components were also observed. The number of interdigitating cell processes decreased and the cell surface microvilli became shortened. Similar ultrastructural alterations were induced by PMA also. All these functional and morphological data strongly support the hypothesis that protein kinase C is a key factor in IFN-mediated cell reactions.
 ...
PMID:Ultrastructural changes of human amniotic cells induced by natural human interferon-alpha. 209 71

Induction of interferon-beta (IFN-beta) in human (BG-9), simian (CV-1) and mouse (L-929) cell lines by Sendai virus and by poly(rI). poly(rC) has been studied for its possible dependence on protein kinase C (PKC) through the use of pharmacological inhibitors (K252a and H-7) of PKC. Exposure of BG-9, CV-1 or L-929 cells to K252a (greater than or equal to 0.025 microM), a staurosporine derivative, 24 h before or after induction of IFN with poly(rI).poly(rC), inhibited by greater than 95% the production of IFN-beta. In contrast, virus-induced IFN production was enhanced threefold or more by K252a in BG-9 and L-929 but not in CV-1 cells. A naphthalene sulphonamide inhibitor of PKC, H-7, at greater than or equal to 5 microM, decreased poly(rI).poly(rC)-induced IFN production in BG-9 and CV-1 cells by 75 to 94%, but had no effect on IFN production in L-929 cells. Viral induction of IFN was not affected significantly by H-7 in BG-9, CV-1 and L-929 cells. In contrast to these results, the calmodulin inhibitor, trifluoperazine (5 to 15 microM) did not affect IFN-beta production by poly(rI).poly(rC) but significantly enhanced IFN production by Sendai virus in both human and murine cell lines. Thus, in human and simian fibroblasts the induction of IFN-beta by poly(rI).poly(rC) appears to be PKC-dependent, whereas viral induction of IFN-beta is not. Results with K252a implicate PKC in non-viral induction of IFN in mouse fibroblasts, as well. Direct measurements of PKC activity in BG-9 cells exposed to several concentrations of K252a showed that the membrane PKC activity is significantly more sensitive to inhibition by K252a than is cytosolic PKC activity. In L-929 cells, K252a inhibited membrane PKC activity similarly, but was less effective as an inhibitor of cytosolic enzyme activity than in BG-9. These studies support an integral role for PKC activity, particularly membrane-associated activity, in non-viral [poly(rI).poly(rC)] induction of IFN-beta in human, simian and mouse fibroblasts.
 ...
PMID:Effect of protein kinase C inhibitors on interferon-beta production by viral and non-viral inducers. 217 82

Leukocytes from mite-sensitive asthmatic patients were challenged with an allergen and the supernatant assayed for histamine, immunoreactive leukotriene C4 (i-LTC4), and gamma-interferon (gamma-IFN). In addition, the concentration of gamma-IFN in the plasma of patients with bronchial asthma was assayed. Significantly higher concentrations (p less than 0.01) of gamma-IFN were detected in patients' plasma (0.27 +/- 0.32 U/ml, n = 61) than in that of healthy controls (0.04 +/- 0.06 U/ml, n = 19). The leukocytes produced 7.3 +/- 6.7 ng of i-LTC4/10(6) basophils (n = 32), and histamine release was 41.1 +/- 37.1% of total histamine. There was a significant correlation (p less than 0.01) between the capacity of leukocytes to release i-LTC4 and gamma-IFN. The capacity of leukocytes to release histamine and to produce gamma-IFN was not significantly correlated (r = 0.263). About twice as much i-LTC4 was generated from leukocytes pretreated for 24 h with 0.1-1.0 U/ml of recombinant human gamma-IFN, but histamine release was not changed. Another type of IFN, alpha-IFN, did not alter the capacity of leukocytes to release histamine as well as gamma-IFN upon preincubation for 24 h at 1-1,000 U/ml. Pretreatment with 1-10 U/ml of beta-IFN slightly enhanced the capacity upon challenge with 10 ng/ml of mite allergen. The enhancing effect of gamma-IFN on i-LTC4 generation was decreased by treatment with H-7, a nonspecific inhibitor of protein kinase C activity.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Augmentation of leukotriene C4 production by gamma interferon in leukocytes challenged with an allergen. 246 47

Treatment of human amniotic cells (UAC) with Cytodex 1 (DEAE-dextran) results in the development of an antiviral state of the cells, as proven by studying (i) the cytopathic effect and (ii) [3H]uridine incorporation into the RNA of vesicular stomatitis virus (VSV) after VSV infection. The same treatment transiently triggers the breakdown of inositol phospholipids and activates the translocation of protein kinase C (PKC). On the basis of these data it can be suggested that cross-linking of cell surface receptors by a solid carrier bearing covalently bound positive charges may result in IFN-like effects.
 ...
PMID:Interferon (IFN)-like antiviral effect is induced by unspecific cross-linking of cell surface receptors. 246 84

We have studied the ability of human peripheral blood mononuclear cells (PBMC) to produce interferon-alpha (IFN-alpha) and IFN-gamma in the presence of pharmacologic agents known to influence calcium transport or calcium-dependent processes. We have found that the production of human (Hu) IFN-gamma is affected significantly by alterations in calcium flux; however, this influence is dependent upon the nature of the compound used to induce IFN. Inhibitors of protein kinase C decreased yields of IFN-gamma but inhibition of calmodulin did not. The presence of vitamin D3 reduced IFN-gamma titers when PHA and IL-2 were used to induce IFN, but not when ionomycin was used as the inducer. The production of IFN-gamma by PBMC was reduced by diminished concentrations in extracellular calcium but not extracellular magnesium. In contrast, neither the presence of any of the pharmacological agents tested above nor the reduction of the calcium concentration influenced the production of HuIFN-alpha by PBMC.
 ...
PMID:Calcium and the production of interferon by human peripheral blood mononuclear cells. 246 90

In this study we report that pretreatment of human amniotic (WISH) cells with interferon gamma (IFN-gamma) in the presence of 12-O-tetradecanoylphorbol 13-acetate (TPA) resulted in the down-modulation of epidermal growth factor (EGF) receptors with respect to both receptor number and affinity. Scatchard analysis of EGF binding in the absence of both IFN-gamma and TPA indicated biphasic binding whereas addition of TPA resulted in the loss of the higher affinity class of sites. Pretreatment with IFN-gamma for 24 h enhanced the TPA-induced inhibition of EGF binding whereas IFN-gamma alone had no effect on binding. Protein kinase C (Ca2+/phospholipid-dependent enzyme) was examined as a possible mediator of IFN-induced EGF-receptor modulation; pretreatment of cells with IFN-gamma affected neither the binding of [3H]phorbol 12,13-dibutyrate to membrane or cytosolic fractions nor the protein kinase C activity, suggesting that IFN-gamma pretreatment did not result in translocation or activation of protein kinase C.
 ...
PMID:Phorbol ester and interferon-gamma modulation of epidermal growth factor receptors on human amniotic (WISH) cells. 249 78


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>