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)

The CDw50 antigen is a constitutively non-phosphorylated leukocyte surface molecule which becomes highly phosphorylated in all the normal and lymphoblastoid cells analyzed (peripheral blood mononuclear cells, Molt 4, CEM, 8402, Namalwa), after stimulation with tumor promoter agents (phorbol 12-myristate 13-acetate, phorbol 12,13-dibutyrate, mezerein). This phosphorylation is rapid (within 1-5 min), dose-dependent and results in the incorporation of PO(3-)4 groups on serine residues. Furthermore, the level of CDw50 phosphorylation induced by tumor promoter agents is decreased by the protein kinase C inhibitors staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine. Activation of peripheral lymphocytes with concanavalin A, phytohemagglutinin and cross-linking of CD3 molecules also induces CDw50 phosphorylation, but the response is delayed and less intense than when tumor promoting agents are used. Treatment with any of the aforementioned agents is not accompanied by quantitative changes in the CDw50 surface expression. We therefore conclude that protein-kinase-C-mediated mechanisms are involved in phosphorylation, but not in regulation of the surface expression of the CDw50 leukocyte antigen.
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PMID:Effect of protein kinase C activators on the phosphorylation and the surface expression of the CDw50 leukocyte antigen. 173 Feb 38

Abnormal regulation of airway glycoprotein secretion may underlie many respiratory diseases. Experimental activation of the protein kinase C (PKC) family of cytosolic enzymes has been shown to induce a secretory response in many tissues. To estimate the effect of PKC activation on airway secretion, alteration in the amount of radiolabeled respiratory glycoconjugate (RGC) released into culture media was determined following feline airway explant exposure to PKC activating agents. Exposure to two known activators of PKC, phorbol 12-myristate 13-acetate (PMA) and mezerein (MEZ), resulted in profound increases in respiratory glycoconjugate release over a seven day experimental period. The response evolved over several hours and was dose dependent. Maximal RGC release, 90% above control, occurred 2 days after exposure to either PMA or MEZ. Pharmacological inhibition of the PKC effect using two PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine and sphingosine, resulted in dose-dependent antagonism of the maximal PMA (10(-7) M)-stimulated RGC release, suggesting altered PKC activity was responsible for augmenting RGC release. Since altered arachidonic acid metabolism has been implicated in mediating some PKC effects, eicosanoids were assayed in airway explant supernatants following PMA exposure. Enhanced release of both cyclooxygenase and lipoxygenase pathway products was detected by radioimmunoassay. Cotreatment of explants with PMA and an inhibitor of oxidative arachidonic acid metabolism, nordihydroguaiaretic acid, blocked RGC release. These data demonstrate prolonged augmentation of respiratory glycoconjugate release from airway explants following exposure to PKC-activating agents.
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PMID:Effect of protein kinase C activating agents on respiratory glycoconjugate release from feline airways. 176 62

The effect of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), an inhibitor of protein kinase C, on the nuclear binding of [3H]dexamethasone and on the phosphorylation of glucocorticoid receptor was studied in rat liver slices to ascertain the role of protein kinase C in the expression of glucocorticoid action. H-7 reduces the nuclear binding of [3H]dexamethasone in rat liver slices. It does not affect the extent of phosphorylation of glucocorticoid receptor both in the absence or in the presence of glucocorticoid. These findings indicate that protein kinase C may be involved in the nuclear binding of glucocorticoid receptor but does not directly influence the receptor phosphorylation.
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PMID:H-7 reduces the nuclear binding of [3H]dexamethasone in rat liver slices but does not affect the phosphorylation of glucocorticoid receptor. 178 14

We examined the potential role of protein kinase C in signal transduction induced by gastrin's stimulation of rat colonic epithelium. Protein synthesis ([35S]methionine incorporation into protein) and enzyme activity (decrease in the cytosolic activity) were measured following epithelial stimulation with gastrin. Gastrin (10 nM) increased [35S]methionine incorporation into protein to 265% above maintenance level. The effect of gastrin was comparable to the stimulation induced by phorbol 12-myristate, 13-acetate (PMA), a strong activator of protein kinase C. The increase in protein synthesis induced by gastrin was totally abolished by 1-(5-isoquinolinyl)-2-methylpiperazine, an inhibitor of protein kinase C activity. Gastrin also decreased the cytosolic activity of the enzyme, an index of its activation and subsequent translocation to other cellular compartments. Therefore, we conclude that gastrin may be acting through a protein kinase C mechanism.
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PMID:Possible involvement of protein kinase C in mediating gastrin-induced response in rat colonic epithelium. 180 Sep 56

12(S)-hydroxyeicosatetraenoic acid (12[S]-HETE) and 13(S)-hydroxyoctadecadienoic acid (13[S]-HODE), lipoxygenase metabolites of arachidonic acid and linoleic acid, respectively, previously have been suggested to regulate tumor cell adhesion to endothelium during metastasis. Adhesion of rat Walker carcinosarcoma (W256) cells to a rat endothelial cell monolayer was enhanced after treatment with 12(S)-HETE and this 12(S)-HETE enhanced adhesion was blocked by 13(S)-HODE. Protein kinase inhibitors, staurosporine, calphostin C, and 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine, inhibited the 12(S)-HETE enhanced W256 cell adhesion. Depleting W256 cells of protein kinase C (PKC) with phorbol 12-myristate-13-acetate abolished their ability to respond to 12(S)-HETE. Treatment of W256 cells with 12(S)-HETE induced a 100% increase in membrane-associated PKC activity whereas 13(S)-HODE inhibited the effect of 12(S)-HETE on PKC translocation. High-performance liquid chromatographic analysis revealed that in W256 cells 12-HETE and 13-HODE were two of the major lipoxygenase metabilites of arachidonic acid and linoleic acid, respectively. Therefore, these two metabolites may provide an alternative signaling pathway for the regulation of PKC. Further, these findings suggest that the regulation of tumor cell adhesion to endothelium by 12(S)-HETE and 13(S)-HODE may be a PKC-dependent process.
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PMID:Lipoxygenase metabolites of arachidonic and linoleic acids modulate the adhesion of tumor cells to endothelium via regulation of protein kinase C. 180 23

In attempt to study the mechanism of F(-)-induced, osteoblast-mediated bone formation, we tried to show the characteristics of Al-F complex-induced mitogenesis in osteoblastic cells. The MOB 3-4-F2 cell line, an osteoblast-like cell line derived from neonatal mouse calvaria, responded to F- (1-2 mM) combined with Al3+ and epidermal growth factor (EGF, 0.01-100 ng/ml) with increased DNA synthesis. Of the several types of Al-F complexes, AlF4- is thought to act as a mitogenic factor. On the other hand, NaF at high concentrations (greater than 2 mM) markedly decreased cell viability. The AlF(4-)-stimulated DNA synthesis at least with a delay of 48 hr, while EGF stimulated DNA synthesis within a few hours (4-6 hr). Both 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and staurosporine, inhibitors of protein kinase C (PKC), further enhanced DNA synthesis in AlF(4-)-treated cells, whereas 12-O-tetradecanoyl-13-acetate (TPA), an activator of PKC, decreased the DNA synthesis. In EGF-treated cells, staurosporine and TPA, but not H-7, decreased DNA synthesis. In addition, indomethacin, an inhibitor of cyclooxygenase, partly inhibited the EGF-induced mitogenesis, which, however, was restored by addition of PGE2. AlF4-, as well as EGF, stimulated the release of arachidonic acid and its metabolites. Indomethacin failed to inhibit the AlF(4-)-induced mitogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aluminofluoride- and epidermal growth factor-stimulated DNA synthesis in MOB 3-4-F2 cells. 180 46

A protein kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) increased lipoprotein lipase (LPL) activity in isolated rat fat pads in a time- and dose-dependent manner. The incubation of H-7 with partially purified LPL did not affect its activity. Under the marked inhibition of protein synthesis by cycloheximide, H-7 still showed a full effect on the increase in LPL activity. A slight but significant increase in LPL activity in the fat pads was observed with inhibitors of cyclic nucleotide-dependent protein kinase. H-7, therefore, may increase LPL activity through processes other than the direct activation of the LPL molecule, or the stimulation of LPL molecule synthesis; probably through a decrease in the activity of protein kinases, especially protein kinase C.
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PMID:Protein kinase inhibitor H-7 increases lipoprotein lipase activity in isolated rat fat pads. 180 58

Tumor-promoting phorbol esters, e.g., 12-O-tetradecanoylphorbol 13-acetate (TPA), inhibit TSH-stimulated iodide organification in vitro implying a role for protein kinase C (PKC) in the regulation of differentiated thyroid function. To further explore the PKC dependence of this action of TPA, we studied the effects of PKC inhibition and downregulation on phorbol-mediated differentiated thyroid function in vitro. In addition, the effects of the nonphorbol PKC activator, phospholipase C (PLC) were studied. TPA (100 nM) inhibited TSH-stimulated iodide organification in cultured porcine thyroid cells by over 95% and caused PKC translocation in vitro. Exogenous PLC (1 U/mL) could mimic these effects of TPA. The PKC inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) inhibited TSH-stimulated iodide organification at concentrations exceeding 10 microM. However, partial recovery of phorbol- and PLC-inhibited iodide organification was seen in the presence of identical concentrations of H7. H7 had no effect on PKC translocation in porcine thyroid cell extracts. After 24 h of TPA treatment to induce PKC downregulation, no recovery of TSH-stimulated iodide organification was observed, suggesting that the effects of TPA were irreversible. These studies indicate that the effects of TPA and PLC on differentiated thyroid function are mediated, at least in part, by PKC. These findings provide further evidence for a role for PKC in the regulation of differentiated thyroid function.
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PMID:Phorbol ester and phospholipase C-mediated differentiated thyroid function in vitro: the effects of protein kinase C inhibition and downregulation. 182 67

In human immunodeficiency virus-1 (HIV-1)-infected cell cultures, cell-to-cell fusion and the formation of multinucleated giant cells (syncytia) are induced as a consequence of interactions between the viral envelope glycoprotein on infected cells and cell surface CD4 molecules on uninfected cells. Although activated CD4+ T cells rapidly form syncytia when cultured with HIV-1 envelope glycoprotein expressing (env+) cells, freshly isolated, unstimulated CD4+ T cells do so more slowly. In these studies, we sought to explore the role of T cell activation in rendering CD4+ T cells susceptible to HIV-1-mediated syncytia formation. Our results indicate that within 2 h of exposure to immunologic stimuli, CD4+ T cells acquire the ability to form syncytia with HIV-1 env+ cells. Both cholera toxin, an inhibitor of protein kinase C (PKC) through its effects on inositol triphosphate and diacylglycerol production, and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride, a noncompetitive inhibitor (with respect to ATP) of PKC, prevented unstimulated but not previously stimulated CD4+ T cells from forming syncytia with HIV-1 env+ cells. 1-Oleoyl-2-acetyl glycerol, an analog of the PKC activator, diacylglycerol, enhanced syncytia formation whereas ionomycin, a calcium ionophore, had no effect. These results suggest that activation of PKC is essential for previously unstimulated CD4+ T cells to become fusogenic.
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PMID:Early activation events render T cells susceptible to HIV-1-induced syncytia formation. Role of protein kinase C. 182 86

The T cell receptor (TcR) heterodimer of alpha/beta glycoprotein is noncovalently associated with CD3 glycoprotein forming TcR/CD3 complex. The TcR have been shown to recognize antigen, and CD3 antigen is responsible for signal transduction. In this study we compared the effects of WT31 (defining alpha/beta TcR) monoclonal antibody (MoAb) and anti-CD3 MoAb on various steps of human T cell activation. Both antibodies depolarized plasma membranes, increased cell volume, induced IL-2 production and the expression of IL-2 receptors (CD25 antigen) and induced DNA synthesis. Furthermore, the two antibodies showed no synergistic effect on any of these parameters. However, both MoAb showed synergism with phorbol ester (PMA). WT31-induced T cell activation was Ca(2+)-dependent because the addition of EGTA to the medium inhibited DNA synthesis and CD25 antigen expression. The blockers of protein kinase C (PKC), 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) and staurosporin, in a dose-dependent manner inhibited WT31-induced DNA synthesis. Cholera toxin but not the pertussis toxin inhibited WT31-induced T cell activation, suggesting involvement of G protein in WT31-induced T cell activation. These data indicate that WT31 antibody activates human T cells by a pathway that is similar to that of anti-CD3-induced T cell activation.
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PMID:T cell activation via the T cell receptor: a comparison between WT31 (defining alpha/beta TcR)-induced and anti-CD3-induced activation of human T lymphocytes. 182 55


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