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)

Adhesion of human salivary gland (HSG) epithelial cells to fibronectin- or collagen I gel-coated substrates, mediated by beta1 integrins, has been shown to upregulate the expression of more than 30 genes within 3-6 h. Adhesion of HSG cells to fibronectin or collagen I for 6 h also enhanced total protein kinase C (PKC) activity by 1.8-2.3-fold. HSG cells expressed PKC-alpha, gamma, delta, epsilon, mu, and zeta. Adhesion of HSG cells to fibronectin or collagen I specifically activated PKC-gamma and PKC-delta. Cytoplasmic PKC-gamma and PKC-delta became membrane-associated, and immunoprecipitated PKC-gamma and PKC-delta kinase activities were enhanced 2.5-4.0-fold in HSG cells adherent to fibronectin or collagen I. In addition, adhesion of fibronectin-coated beads to HSG monolayers co-aggregated beta1 integrin and PKC-gamma and PKC-delta but not other PKC isoforms. Thus, integrin-dependent adhesion of HSG cells to fibronectin or collagen I activated PKC-gamma and PKC-delta. The role of this PKC upregulation on adhesion-responsive gene expression was then tested. HSG cells were treated with the specific PKC inhibitor bisindolylmaleimide I, cultured on non-precoated, fibronectin- or collagen I-coated substrates, and analyzed for changes in adhesion-responsive gene expression. Bisindolylmaleimide I strongly inhibited the expression of seven adhesion-responsive genes including calnexin, decorin, S-adenosylmethionine decarboxylase, steroid sulfatase, and 3 mitochondrial genes. However, the expression of two adhesion-responsive genes was not affected by bisindolylmaleimide I. Treatment with bisindolylmaleimide I did not affect cell spreading and did not significantly affect the actin cytoskeleton. These data suggest that adhesion of HSG cells to fibronectin or collagen I induces PKC activity and that this induction contributes to the upregulation of a variety of adhesion-responsive genes.
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PMID:Adhesion of epithelial cells to fibronectin or collagen I induces alterations in gene expression via a protein kinase C-dependent mechanism. 1157 7

In analyzing the regulation of neurotrophin production/secretion from microglia, C8-ceramide (D-erythro-sphingosine, N-octanoyl-) was found to induce secretion of brain-derived neurotrophic factor (BDNF) from microglia in vitro. In the present study, the action of C8-ceramide in secreting neurotrophic and harmful factors was investigated and compared with the effects of lipopolysaccharide (LPS). C8-ceramide as well as LPS enhanced the production/secretion of BDNF but, different from LPS, did not induce tumor necrosis factor alpha, interleukin-1beta, or nitric oxide. The C8-ceramide-induced BDNF release was significantly suppressed by protein kinase C (PKC) inhibitor, bisindolylmaleimide, which targets PKC isoforms, alpha, beta, gamma, delta and epsilon. However, it was not suppressed by a specific inhibitor of PKCalpha. Furthermore, PKCbeta and gamma were undetected in the microglia. Therefore, PKCdelta and/or epsilon appear to be functioning PKC isoforms. In contrast, none of the mitogen-activated protein kinases (MAPKs) and none of the transcription factors, including the cAMP response element-binding transcription factor (CREB) and nuclear factor kappaB (NFkappaB) were activated in the microglia in response to C8-ceramide. These results indicate that ceramide-induced BDNF release in microglia is mediated by a signaling pathway associated with PKCdelta and/or epsilon, but not with activation of MAPKs, CREB and NFkappaB.
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PMID:Ceramide activates microglia to enhance the production/secretion of brain-derived neurotrophic factor (BDNF) without induction of deleterious factors in vitro. 1184 76

T-cell biological responses appear to involve the complex interaction of T-cell surface receptors, intracellular signaling molecules and the cytoskeleton. Both the serine/threonine protein kinase families protein kinase C (PKC) and protein kinase B or RAC-PK (AKT/PKB) have been implicated in signal transmission leading to activation, differentiation as well as cellular survival of T-lymphocytes. The PKC gene family consists of nine diverse isotypes (PKC alpha, beta, gamma, delta, epsilon, xi, eta, theta; and iota), the AKT/PKB gene family includes three kinases (AKT1/PKB alpha, AKT2/PKB beta, AKT3/PKB gamma). Here, we attempt to summarize the regulation as well as downstream signaling pathways of PKC and AKT/PKB isotypes, that may act additive in TCR/CD28 induced proliferation and survival of peripheral CD4+ T-lymphocytes.
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PMID:Protein kinase C and AKT/protein kinase B in CD4+ T-lymphocytes: new partners in TCR/CD28 signal integration. 1204 76

Enzymes belonging to the protein kinase C (PKC) family represent one of the major mediators of signal transduction in melanocytes. To identify PKC isoforms that may be associated with the process of malignant transformation and metastasis, we investigated the expression pattern of 11 different PKC isoforms (alpha, beta I, beta II, gamma, delta, epsilon, eta, theta, zeta, lambda, and iota) in melanoma lymph node metastases, in cell lines established from these metastases, in primary cell cultures from normal melanocytes, and in permanent cell lines established from spontaneously transformed melanocytes. PKC alpha, beta I, beta II, delta, epsilon, eta, zeta, lambda and iota were found to be expressed in total lysates from melanoma metastases. In permanent cell lines established from these metastases, the expression levels of PKC beta I, beta II, delta, epsilon, and eta were lower or undetectable when compared with initial expression in tumour lysates. In normal primary melanocyte cultures, the PKC isoforms beta II, delta, epsilon, eta and iota were undetectable. PKC gamma and theta isoforms were undetectable in all melanocytic cell types examined. PKC iota was the only isoform exclusively detected in tumour lysates, in spontaneously transformed melanoma cells and melanoma cell lines, but not in normal melanocytes, and may therefore be associated with the transformed phenotype in human melanoma in vitro and in vivo.
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PMID:Protein kinase C isoforms in normal and transformed cells of the melanocytic lineage. 1214 Mar 76

Apoptosis plays a major role in gastrointestinal epithelial cell turnover. We have examined induction of apoptosis by Helicobacter pylori in gastric AGS cells and the role of protein kinase C (PKC) which has been shown to modulate programmed cell death. Incubation of AGS cells with H. pylori resulted in an activation of caspases 3 and 9 and induced programmed cell death. The PKC activator 12- O -tetradecanoylphorbol-13-acetate (TPA) caused translocation of PKC gamma, delta and var epsilon, prevented H. pylori -induced caspase activation and programmed cell death. Cocultivation of AGS cells with H. pylori resulted in a translocation of the atypical PKC isoform PKC lambda. We suggest that inhibition of H. pylori induced apoptosis by PKC activation can play a role in the process of neoplastic transformation.
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PMID:Helicobacter pylori -induced apoptosis in gastric epithelial cells is blocked by protein kinase C activation. 1238 44

ZEBRA protein converts Epstein-Barr virus (EBV) infection from the latent to the lytic state. The ability of ZEBRA to activate this switch is strictly dependent on the presence of serine or threonine at residue 186 of the protein (A. Francis, T. Ragoczy, L. Gradoville, A. El-Guindy, and G. Miller, J. Virol. 72:4543-4551, 1999). We investigated whether phosphorylation of ZEBRA protein at this site by a serine-threonine protein kinase was required for activation of an early lytic cycle viral gene, BMRF1, as a marker of disruption of latency. Previous studies suggested that phosphorylation of ZEBRA at S186 by protein kinase C (PKC) activated the protein (M. Baumann, H. Mischak, S. Dammeier, W. Kolch, O. Gires, D. Pich, R. Zeidler, H. J. Delecluse, and W. Hammerschmidt, J. Virol 72:8105-8114, 1998). Two residues of ZEBRA, T159 and S186, which fit the consensus for phosphorylation by PKC, were phosphorylated in vitro by this enzyme. Several isoforms of PKC (alpha, beta(1), beta(2), gamma, delta, and epsilon ) phosphorylated ZEBRA. All isoforms that phosphorylated ZEBRA in vitro were blocked by bisindolylmaleimide I, a specific inhibitor of PKC. Studies in cell culture showed that phosphorylation of T159 was not required for disruption of latency in vivo, since the T159A mutant was fully functional. Moreover, the PKC inhibitor did not block the ability of ZEBRA expressed from a transfected plasmid to activate the BMRF1 downstream gene. Of greatest importance, in vivo labeling with [(32)P]orthophosphate showed that the tryptic phosphopeptide maps of wild-type ZEBRA, Z(S186A), and the double mutant Z(T159A/S186A) were identical. Although ZEBRA is a potential target for PKC, in the absence of PKC agonists, ZEBRA is not constitutively phosphorylated in vivo by PKC at T159 or S186. Phosphorylation of ZEBRA by PKC is not essential for the protein to disrupt EBV latency.
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PMID:Disruption of Epstein-Barr virus latency in the absence of phosphorylation of ZEBRA by protein kinase C. 1238 79

The involvement of PKC isoform in the methamphetamine (MA)-induced death of neuron-like PC12 cell was studied. The death and the enhanced terminal dUTP nick end labeling (TUNEL) staining were inhibited by a caspase inhibitor, z-Val-Ala-Asp- (OMe)-CH(2)F (z-VAD-fmk). However, the cell death shows neither morphological nor biochemical features of apoptosis or necrosis. The cell death was suppressed by a protein kinase C (PKC) activator, 12,13-phorbol myristate acetate, but was enhanced by PKC specific inhibitor calphostin C or bisindolylmaleimide, not by PKC inhibitor relatively specific for PKC-alpha (safingol) or PKC-delta (rottlerin). Western blotting demonstrated the expression of PKC-alpha, gamma, delta, epsilon and zeta, of which PKC-epsilon translocated from the soluble to the particulate fraction after MA-treatment. Antisense to PKC-epsilon enhanced MA-induced death. A glutamate receptor antagonist MK801 abrogated the cell death, which is reversed by PKC inhibition. These data suggest that PKC-epsilon promotes PC12 cell survival through glutamate receptor suppression.
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PMID:Protein kinase C-epsilon protects PC12 cells against methamphetamine-induced death: possible involvement of suppression of glutamate receptor. 1255 48

It has been previously shown that 5-HT uptake inhibition produced by tetanus toxin (TeTx) corresponds to a non-competitive inhibition, and it is preceded by phosphorylation of the tyrosine-kinase receptor trkA, phospholipase C activation and translocation of protein kinase C isoforms [FEBS Lett. 481 (2000) 177; FEBS Lett. 486 (2000) 136]. In the present work, it is shown that agonists of tyrosine-kinase receptors (NGF, EGF, basic FGF) enhance Na(+)-dependent, 5-hydroxytryptamine (serotonin, 5-HT) uptake in the synaptosomal-enriched P(2) fraction from rat-brain, suggesting a divergence in the intracellular signal pathways triggered by TeTx and by agonists of TyrK receptors. Co-applications of TeTx and agonists of TyrK receptors result in a mutual and partial reversion of their effects on 5-HT transport. In spite of their differences on transport, TeTx, TPA and NGF produce an increase in serotonin transporter phosphorylation in Ser separately, which is abolished by the PKC-inhibitor bisindolylmaleimide-1. Co-application of sodium vanadate, a tyrosine-phosphatase inhibitor, partially abolishes the effect produced by TeTx, whereas genistein, a tyrosine-kinase inhibitor, does not exert any variation of TeTx inhibition. Analyses by immunoblotting of the activation of specific PKC isoforms activation, determined as translocation to the membrane compartment, reveals differences in the pattern produced by NGF and TeTx. PKC gamma, delta, and epsilon isoforms are equally activated by both compounds, whereas the beta isoform is activated in a sustained manner only by TeTx, and the alpha isoform is only down-regulated by NGF. The aim of the present work was to explore whether NGF have the same effect on 5-HT transport than TeTx, since both compounds share the ability of activate part of the same transduction pathways. In spite of this, growth factors and TeTx show an opposite effect on 5-HT transport, even though SERT phosphorylation is enhanced in both cases. The differential effect on alpha- and beta-PKC isoenzymes found between NGF and TeTx action could explain this apparent discrepancy.
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PMID:Serotonin transport is modulated differently by tetanus toxin and growth factors. 1259 Sep 35

We have previously reported that prolonged exposure of porcine coronary arteries to adenosine agonists upregulates protein kinase C (PKC) through the activation of adenosine A1 receptor-coupled to pertussis toxin sensitive G-protein(s) [Am. J. Physiol. 264 (1993) H1465; Am. J. Physiol. 269 (1995) H1619]. The mechanism(s) by which A1 adenosine receptor upregulates PKC (isoforms) are not yet clearly understood. In the present study, we identified the alpha, beta 1, beta 2, gamma, epsilon, and zeta PKC isoforms that were upregulated by adenosine A1 receptor agonist as a possible mechanism(s) involved for this upregulation. Incubation of porcine coronary smooth muscle cells (PCSMC) with adenosine A1 receptor agonist (2s)-N6-[2-endo-norbornyl]adenosine (ENBA) caused an upregulation of PKC (isoforms), which were blocked by adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). Western blot analysis using specific antibodies to PKC isoforms indicated that all the isoforms tested (alpha, beta I, beta II, mu, gamma, delta, epsilon, and zeta) were present in the primary cultured smooth muscle cells from porcine coronary artery. Western blot studies indicated that PKC alpha, beta I, beta II, gamma, epsilon, and zeta isoforms were upregulated in a dose dependent manner by adenosine agonist (ENBA) and PKC delta and mu were not altered.
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PMID:Protein kinase C isoforms and A1 adenosine receptors in porcine coronary smooth muscle cells. 1261 90

An immunocytochemical study using antibodies against p21ras, Raf-1, MAP kinase/ERK1 and PKCalpha, beta, gamma, delta, epsilon, zeta, isoforms were performed on a 20-methylcholanthrene-induced transformed murine embryonal fibroblast cells in both in vitro and in vivo growth conditions. Altered expression of p21ras, Raf-1, MAP kinase in this particular cell line strongly supported the previous findings of the activation of one component of signal transduction under the influence of the other in the MAP kinase cascade of signal transduction during neoplastic transformation and which also seemed to be involved in CNCI-PM-20 cell line. The altered expression of PKCalpha, beta, and delta was thought to be an epigenetic event occurring under the indirect influence of other changes in these cells. Host physiology and metabolism did not have much impact on the expression of these gene products after biological incubation of these cells in syngenic host.
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PMID:Immunocytochemical detection of p21ras, Raf-1, ERK1/MAP kinase and PKC isoforms in a 20-methylcholanthrene-induced transformed murine embryonal fibroblast cells in culture. 1274 Jun 48


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