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

We have previously shown that recombinant murine interferon-gamma, rIFN-gamma, and recombinant human interleukin-1 alpha, rIL-1 alpha, induce differentiation of murine pre-B-like cell line 70Z/3, a finding associated with stimulation of Na+/H+ exchange across the plasma membrane. The present study was designed to test whether the enhanced Na+/H+ exchange is mediated by Ca2+/phospholipid-dependent protein kinase C. The results show that two structurally different peptides, rIFN-gamma and rIL-1 alpha, induce identical patterns of transient translocation of protein kinase C from the cytosol to the membranes. The increase in membrane-associated protein kinase C activity was first detected 20 min after exposure to the lymphokines. This activity peaked at 30 min and was back to baseline by 2 h. At each time point, the increase in membrane-associated protein kinase C activity corresponded to a decrease in the activity of protein kinase C in the cytoplasmic fraction. The total cellular activity (cytosol + membrane) remained the same. Two series of experiments were carried out to test the role of protein kinase C in mediating the lymphokine-stimulated Na+/H+ exchange. In the first, the effects of rIFN-gamma and rIL-1 alpha on cytoplasmic pH were measured in the presence of a protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, H-7. In the second, rIFN-gamma- and rIL-1 alpha-induced cytoplasmic alkalinization was determined in cells containing decreased protein kinase C activity. Under both experimental conditions, lymphokine-induced cytoplasmic alkalinization was not attenuated. These results indicate that, although both rIFN-gamma and rIL-1 alpha cause association of protein kinase C with membranes, activation of protein kinase C is not required for rIFN-gamma or rIL-1 alpha to stimulate Na+/H+ exchange across the plasma membrane.
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PMID:Interferon-gamma and interleukin-1 alpha induce transient translocation of protein kinase C activity to membranes in a B lymphoid cell line. Evidence for a protein kinase C-independent pathway in lymphokine-induced cytoplasmic alkalinization. 313 39

Thrombin stimulated rapid formation of diacylglycerol, inositol 1,4,5-trisphosphate (IP3) and thromboxane B2 (TXB2) in human platelets. Formation of diacylglycerol and IP3 appeared to precede that of TXB2. Activation of protein kinase C by diacylglycerol combining with Ca+2 mobilization by IP3 has been implicated in mediating arachidonate release. However, addition of the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) to platelet suspension did not inhibit thrombin-stimulated arachidonate release and TXB2 synthesis, whereas addition of the Ca+2 antagonist, 3,4,5-trimethoxybenzoic acid 8-(diethylamino) octyl ester (TMB-8) or the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) abolished arachidonate release. The correlation of IP3 production with arachidonate release on increasing the concentrations of thrombin was further examined. IP3 production reached near maximum at 0.2 U/ml, whereas TXB2 synthesis continued to increase at 1 U/ml. These results suggest that protein kinase C activation may not mediate arachidonate release and that Ca+2 mobilization by IP3 may only partially account for arachidonate release in platelets stimulated with relatively high concentrations of thrombin.
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PMID:Does protein kinase C activation mediate thrombin-induced arachidonate release in human platelets? 314 Sep 2

Protein kinase C activators 1,2-oleoylacetylglycerol (OAG, 0.5-50 microM), a synthetic diacylglycerol analog, and phorbol-12,13-dibutyrate (Pb(Bu)2, 0.016-1.6 microM) depressed the calcium (Ca)-dependent components of action potentials in isolated superior cervical ganglion cells of rabbits. Similar depressions were elicited when the M2-muscarinic receptors were activated. This muscarinic modification of the action potential was obscured after the perfusion with protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7, 50 microM). It seems that protein kinase C is an intermediator between the M2-muscarinic receptors and the Ca channels regulating the firing rate of the postganglionic cells.
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PMID:Protein kinase C activators mimic the M2-muscarinic receptor-mediated effects on the action potential in isolated sympathetic neurons of rabbits. 316 15

When raising the extracellular Ca2+ concentration stepwise from 0.5 to 3.0 mM, bovine parathyroid cells reacted with initial transient and sustained elevations of the cytoplasmic Ca2+ concentration (Ca2+i), as well as more than 50% inhibition of parathyroid hormone (PTH) release. Human parathyroid adenoma cells and bovine cells cultured for 1 day or exposed to a low concentration of a monoclonal antiparathyroid antibody exhibited right-shifted dependencies of PTH release and Ca2+i on extracellular Ca2+ and reduced Ca2+i transients. The protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA) further right-shifted the dose response relationship for Ca2+ regulated Ca2+i of the adenoma cells, whereas the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) tended to normalize it, without affecting Ca2+i of normal bovine cells. In cells from an oxyphil adenoma and a parathyroid carcinoma as well as in bovine cells cultured 4 days or exposed to a high concentration of the antiparathyroid antibody, there were no Ca2+i transients, very small increases in steady-state Ca2+i and nonsuppressible PTH release. The results suggest that reduced availability of a putative Ca2+-receptor and increased protein kinase C activity may be important factors in the decreased Ca2+ sensitivity of abnormal parathyroid cells.
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PMID:Modulation of the Ca2+-sensing function of parathyroid cells in vitro and in hyperparathyroidism. 334 64

Stimulation of the neutrophils with fMet-Leu-Phe inhibits the rise in intracellular concentration of free calcium produced by the subsequent addition of platelet-activating factor. This deactivation is not observed in pertussis toxin treated cells. In addition, preincubation of the cells with the protein kinase C activator phorbol 12-myristate 13-acetate for three minutes abolishes completely the rise in calcium produced by platelet-activating factor. This inhibition is prevented by the addition of the protein kinase C inhibitor 1-(5-isoquinoline-sulfonyl)-2-methyl piperazine prior to the addition of the phorbol ester. Phorbol 12-myristate 13-acetate, at a concentration that does not produce significant inhibition, accelerates the rate of calcium removal from the cytoplasm, and this is abolished by the protein kinase C inhibitor. In contrast, the deactivation by fMet-Leu-Phe is not prevented by the protein kinase C inhibitor. The results presented here suggest that the protein kinase C system may regulate the opening by platelet-activating factor of possible plasma membrane associated pertussis toxin independent calcium channels and/or the binding of platelet-activating factor to the receptors. In addition, protein kinase C activation increases the rates of the calcium efflux pump and/or calcium sequestering by intracellular organelles. The most simple and straightforward explanation of the observed deactivation by fMet-Leu-Phe is that the addition of fMet-Leu-Phe to neutrophils stimulates the production of platelet-activating factor which then binds to and deactivates the receptors.
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PMID:Intracellular calcium rise produced by platelet-activating factor is deactivated by fMet-Leu-Phe and this requires uninterrupted activation sequence: role of protein kinase C. 334 14

12-O-tetradecanoylphorbol-13-acetate (TPA), a potent tumor promoter, stimulated membrane transport of choline in cultured cells. This is one of the earliest phenomena caused by tumor promoter. 4-O-methyl-TPA and mezerein showed similar stimulatory effects, but 4 beta-phorbol, which has no tumor-promoting activity, did not show any significant effect on choline transport. A calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, inhibited the TPA-stimulated transport of choline, whereas the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine did not. These results suggest that the Ca2+-calmodulin system, but not protein kinase C, may play an important role in the mechanism of this phenomenon.
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PMID:Stimulation of choline transport in cultured cells induced by 12-O-tetradecanoylphorbol-13-acetate: one of the earliest phenomena induced by the tumor promoter. 338 37

Smooth muscle cells isolated from the circular muscle layer of cat esophagus and lower esophageal sphincter (LES) exhibit distinct contractile intracellular signal transduction pathways in response to acetylcholine. To determine whether these contractile pathways are muscle type dependent, the authors examined the signal transduction pathways utilized by substance P and bombesin, which in other tissues, use different signal transduction pathways, and by the GTP analog, guanosine 5'-O-3-thiotriphosphate (GTP gamma S), which activates all available G proteins. Western blot analysis of esophageal and LES circular muscle revealed the presence of Gq-G11 (42 kD), Gi1-Gi2 (40 kD) and Go-Gi3 (40 kD) types of G proteins. The responses of esophageal cells to bombesin and substance P were blocked by 1) a Gi3 protein antibody, 2) the inhibitor of specific phosphatidylcholine-phospholipase C (PLC) D609 potassium tricyclo-[5.2.1.0(2.6)]-decyl-(9[8])-xanthogenate, 3) inhibition of phosphatidic acid phosphohydrolase by propranolol, 4) the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) and 5) incubation in Ca(++)-free medium. Conversely, the responses of LES muscle cells to bombesin and substance P were blocked by 1) a Gq-G11 antibody, 2) a phosphatidylinositol-specific PLC antagonist U-73122 (1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17- yl]amino]hexyl]-1H-pyrrole-2,5-dione), 3) the calmodulin inhibitor CGS9343B (1,3-Dihydro-1-[1-((4-methyl-4H,6H-pyrrolo[1,2-a]-[4,1]benzoxazepin++ +-4 - yl)methyl-4-piperindinyl]-2H-benzimidazol-2-one maleate) and 4) incubation in Sr++. After permeabilization by saponin, inositol 1,4,5-trisphosphate contracted LES but not esophageal cells. The inositol 1,4,5-trisphosphate receptor antagonist heparin and depletion of intracellular Ca++ stores by thapsigargin or A23187 4-Benzoxazolecarboxylic acid, 5-(methylamino)-2-[[3,9,11-trimethyl-8-[1-methyl-2-oxo-2-(1H-pyrrol- 2-yl)ethyl]-1,7-dioxaspiro[5.5]undec-2-yl]methyl]-, [6s-[6.alpha. (2S*,3S*),8.beta. (R*), 9.beta., 11. alpha.]]-(9Cl), blocked bombesin- and substance P-induced contraction of LES but not of esophageal muscle. In addition, contraction in response to GTP gamma S, which activates all G proteins, was blocked in esophageal cells by a Gi3-protein antibody, propranolol, D609 and H7. In LES muscle cells, the response to GTP gamma S was blocked by a Gq protein antibody, U-73122 and CGS934B. These data demonstrate that, in esophageal muscle, different agonists activate the same Gi3 protein, phosphatidylcholine-specific phospholipases and protein kinase C-dependent pathway.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Agonist-independent, muscle-type-specific signal transduction pathways in cat esophageal and lower esophageal sphincter circular smooth muscle. 753 46

The effect of inhibitors and activators of protein kinase C and phospholipase A2 on radiation-induced apoptosis of rat and mouse thymocytes has been studied. It is shown that the apoptosis is prevented by the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperasine dihydrochloride and is potentiated by protein kinase C activator phorbol 12-myristate 13-acetate, calcium ionophore A23187 and concanavalin A. The protein kinase C activators initiate apoptosis in mouse but not in rat thymocytes. The inhibitor of phospholipase A2 prevents apoptosis induced by all the factors. The results obtained indicate that both protein kinase C and phospholipase A2 are involved in the thymocyte apoptosis.
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PMID:Dependence of thymocyte apoptosis on protein kinase C and phospholipase A2. 803 62

Involucrin is one of the precursor proteins of keratinocyte cornified envelope. Although the formation of the cornified envelope is induced by tumor-promoting phorbol esters, the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the involucrin gene expression remains unknown. We have isolated a 5'-upstream region of human involucrin gene and examined its TPA-dependent promoter activity. The involucrin upstream region with the untranslated first exon was connected to chloramphenicol acetyltransferase (CAT)-involucrin promoter expression vector (INV-CAT) and was transfected into fetal rat keratinizing epidermal (FRSK) cells. The INV-CAT-transfected FRSK cells showed considerable CAT activity that was significantly augmented by the treatment of cells with TPA. FRSK cells that were transfected with a reversely oriented 5'-upstream sequence revealed little CAT activity and did not respond to TPA. The effect of TPA was significantly inhibited by the protein kinase C inhibitor 1-(5-isoquinoline-sulfonyl)-2-methyl piperazine dihydrochloride (H-7). Other protein kinase C activators (1-oleoyl-2-acetylglycerol and mezerein) also induced the INV-CAT promoter activity, whereas 4-O-methyl phorbol myristate acetate, a very weak protein kinase C activator, had only a slight effect. Analysis of the nucleotide sequence of the 5'-upstream region detected several 5'-TGANTCAA-3' sequences that are highly conserved TPA-response elements (TRE). Cotransfection of both c-jun and c-fos expression vectors with the INV-CAT vector into FRSK cells resulted in increased CAT activity. Cotransfection of either the c-jun or c-fos vector singly with the INV-CAT vector into FRSK cells had negligible effects. Dexamethasone significantly inhibited the TPA-induced promoter activity in the INV-CAT-transfected FRSK cells. These results indicate that involucrin gene expression is positively controlled by TPA through the activation of the protein kinase C/TRE system.
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PMID:Analysis of the 5'-upstream promoter region of human involucrin gene: activation by 12-O-tetradecanoylphorbol-13-acetate. 838 Aug 29

We investigated the effect of extracellular ATP on the interaction of epidermal growth factor (EGF) with its receptor in cultured renal epithelial cells, LLC-PK1. Pretreatment with ATP, but not adenosine, inhibited the binding of 125I-labeled EGF. The inhibition demonstrated by ATP resulted from a decrease in the affinity of EGF receptors for its ligand, with no change in the number of EGF receptors. Incubation of phorbol 12-myristate 13-acetate (PMA) for 30 min mimicked the ATP-mediated inhibition. On the other hand, prolonged pretreatment with PMA, which leads to disappearance of protein kinase C activity, reversed the inhibition. In addition, pretreatment with the protein kinase C inhibitor 1-(5-isoquinoline sulfonyl)-2-methylpiperazine prevented the ATP-mediated inhibition. ATP triggered an increase in inositol 1,4,5-trisphosphate levels and translocation of protein kinase C from cytosol to membranes, consist with the stimulation of phospholipase C and the activation of protein kinase C. These results demonstrate that extracellular ATP attenuates the ligand binding affinity of EGF receptor via the stimulation of phospholipase C, leading to the activation of protein kinase C in the LLC-PK1 cells.
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PMID:Extracellular ATP-induced regulation of epidermal growth factor signaling in cultured renal LLC-PK1 cells. 847 24


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