Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The parenteral administration of a single dose of 3-methylcholanthrene to rats caused an increase in the liver of the concentration of 3', 5'-cAMP and of the activity of cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). These events were followed by an increased activity of ornithine decarboxylase (L-ornithine carboxy-lase, EC 4.1.1.17), the enzyme that controls the biosynthesis of polyamines. Finally, the activity of benzo[a]pyrene hydroxylase, as well as the amount of cytochrome P-448, was increased. Similarly, after the administration of phenobarbital, there was first an increase in the cAMP concentration and in the activity of cAMP-dependent protein kinase, then the induction of ornithine decarboxylase, and finally, an enhanced activity of ethylmorphine N-demethylase and an increased content of cytochrome P-450. These data suggest that the drug-induced processes in liver that increase the activities of the oxidative, and presumably other, drug-metabolizing enzymes include the following sequence of events: (1) increase in cAMP concentration and/or activation of cAMP-dependent protein kinase; (2) induction of ornithine decarboxylase; and, (3) induction of drug-metabolizing enzymes.
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PMID:Activation of 3':5'-cyclic AMP-dependent protein kinase and induction of ornithine decarboxylase as early events in induction of mixed-function oxygenases. 17 81

Stimuli known to induce tyrosine aminotransferase in H35 cells were tested relative to their ability to induce ornithine decarboxylase, the initial enzyme in the polyamine biosynthetic pathway. Dibutyryl cyclic AMP (0.5 mM), parachlorophenylthio-cyclic AMP (0.1 mM) and dexamethasone (1 muM) stimulated the activity of ornithine decarboxylase 7- to 8-fold by 5 hr of induction. There was a delay of 1 hr before any increase in enzyme activity was detectable. Insulin administered alone failed to significantly change ornithine decarboxylase activity. The ability of dibutyryl cyclic AMP to elevate ornithine decarboxylase activity was found to be concentration-dependent, and a dose-response relationship very similar to that for the induction of tyrosine aminotransferase by dibutyryl cyclic AMP was observed in these cells. The ability of various 8-substituted cyclic AMP analogues to increase the activity of ornithine decarboxylase was correlated with their ability to activate purified protein kinase.
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PMID:Induction of ornithine decarboxylase in Reuber H35 rat hepatoma cells. 18 23

Incubation of S49 lymphoma cells with N6,O2'-dibutyryl cyclic AMP (Bt2cAMP) decreases the activities of ornithine decarboxylase (L-ornithine carboxy-lyase; EC 4.1.1.17) and S-adenosylmethionine decarboxylase (S-adenosyl-L-methionine carboxy-lyase; EC 4.1.1.50), the two principal enzymes in the pathway of polyamine synthesis. This decrease is dose-dependent, commences after a 3-hr delay, virtually abolishes the assayable activities of the two enzymes, and is not associated with a soluble inhibitor of the enzyme activities. Studies in mutant S49 clones that have altered protein kinase indicate that cAMP-dependent protein kinase mediates the decreases in enzyme activities. The dose-response pattern for the cAMP-stimulated decrease in enzyme activities parallels the pattern for the cAMP-stimulated, cell cycle-specific (G1) growth arrest of S49 cells. The activity of ornithine decarboxylase decreases faster than Bt2cAMP arrests wild-type S49 cells and, similarly, release of cells from the cAMP-stimulated arrest in G1 increases the activity of ornithine decarboxylase faster than cells exit from G1. These findings contrast with reports that cAMP induces ornithine decarboxylase in other cell types and further suggest that passage of cells through cell cycle is required for maintaining the activities of ornithine and S-adenosylmethionine decarboxylases.
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PMID:Cyclic AMP-dependent protein kinase mediates a cyclic AMP-stimulated decrease in ornithine and S-adenosylmethionine decarboxylase activities. 20 37

A single dose of growth hormone (10 mg/kg, i.p.) was injected into male weanling rats (50--60 g), and the temporal changes in cyclic AMP concentration, protein kinase activation, and ornithine decarboxylase activation were measured in the liver and adrenal gland. The level of cyclic AMP did not change significantly from control values in either liver or adrenal following growth hormone administration. Cyclic AMP-dependent protein kinase(s); however, was markedly activated in liver and adrenal within 30 min. Protein kinase remained activated for more than 4 hr in the liver, while activation of protein kinase in the adrenal returned to control value within 2 hr. Ornithine decarboxylase activity was elevated 20-fold in liver within 4 hr of injection and was increased 7- to 8-fold in be adrenal within l hr. These observations are discussed with regard to the generality of the role of cyclic AMP as the second messenger for target-specifici trophic hormone action and the significance of protein kinase activiation as an index of the cyclic nucleotide involvement in the growth response.
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PMID:Activation of cyclic AMP-dependent protein kinase(s) by growth hormone in the liver and adrenal gland of the rat. 20 62

After a single injection of diethylnitrosamine (200 mg/kg), there was a rapid increase in the activity ratio of hepatic cyclic adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase (within 1 hr) followed by the induction of ornithine decarboxylase which was detectable by 3 hr. Both the cyclic AMP-dependent protein kinase activity ratio and the activity of ornithine decarboxylase were significantly elevated above controls for 7 days following the administration of diethylnitrosamine. A single noncarcinogenic dose of diethylnitrosamine (25 mg/kg) did not increase the cyclic AMP-dependent protein kinase activity ratio or induce ornithine decarboxylase activity at 24 hr postadministration. However, serial administration of diethylnitrosamine (25 mg/kg) for 4 or 7 days resulted in an increased activity ratio of cyclic AMP-dependent protein kinase and increased ornithine decarboxylase activity. This is the first report of a prolonged increase in both the activity ratio of hepatic cyclic AMP-dependent protein kinase and the activity of ornithine decarboxylase in response to a single carcinogenic dose of diethylnitrosamine.
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PMID:Prolonged induction of hepatic ornithine decarboxylase and its relation to cyclic adenosine 3':5'-monophosphate-dependent protein kinase activation after a single administration of diethylnitrosamine. 22 43

Cholera toxin activated beef thyroid cyclic AMP-dependent protein kinase in a dose (0.2 to 8 microgram/ml)-related fashion. Thus, when beef thyroid slices were incubated with toxin (8 microgram/ml) for 90 minutes and then assayed for protein kinase, the activity ratio (i.e. -cyclic AMP/+cyclic AMP) increased from 0.32 +/- 0.02 to 0.77 +/- 0.06. The toxin (5 microgram/ml)-induced increase was abolished by inclusion of ganglioside GM1 in the incubation medium (I50, 0.7 microgram/ml), whereas, gangliosides GD1a and GT1 were without effect. In contrast, TSH-activated protein kinase was unaffected by ganglioside addition. Cholera toxin increased rat thyroid ornithine decarboxylase (ODC) activity in-vitro in a dose (0.1 to 10 microgram/ml)-related fashion [basal, 100 cf cholera toxin (10 microgram/ml), 1500 pmol 14CO2/g tissue/30 min]. The toxin (1 microgram/ml)- (but not TSH-) induced increase in ODC was abolished by inclusion of ganglioside Ga and GT1 were without effect. Cholera toxin stimulation of ODC was inhibited by indomethacin or iodide as are the stimulatory effects of TSH or dibutyryl cyclic AMP. These results demonstrate that although there are differences in the TSH and cholera toxin responses with respect to receptor (ganglioside) interaction, they nevertheless elicit similar intracellular responses in thyroid.
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PMID:Effects of cholera toxin on thyroid cyclic AMP-dependent protein kinase and ornithine decarboxylase activities. 22 45

Chemoprevention of colon cancer is emerging as an alternative to therapy with a broad potential for reducing cancer incidence in defined high-risk groups and the general population. Besides several chemopreventive agents in use and under investigation, D,L-alpha-difluoromethylornithine (DFMO) and piroxicam have been shown to effectively inhibit colon carcinogenesis in rodents. A variety of proliferation-related parameters have been suggested as potential intermediate markers of cancer risk that could be used to monitor the progress of chemoprevention in clinical trials. We have investigated the effect of chemopreventive agents, DFMO, and piroxicam on mucosal ornithine decarboxylase (ODC) and tyrosine-specific protein kinase (TPK) activities during different stages of azoxymethane (AOM)-induced colonic carcinogenesis in male F344 rats in order to examine the plausibility of using these enzymes as intermediate biochemical markers of colon cancer. Groups of male F344 rats were fed modified AIN-76A diets containing 0 or 150 ppm piroxicam or 4000 ppm DFMO and given s.c. injections of AOM dissolved in normal saline at a dose of 15 mg/kg body weight/week, once weekly, for 4 weeks. Vehicle control groups received s.c. equal volumes of normal saline. Groups of animals were then sacrificed at 0, 4, 16, 24, and 32 weeks after AOM or saline treatment, and their colonic mucosa was analyzed for ODC and TPK activities. AOM treatment significantly increased mucosal ODC as well as TPK activities. AOM-induced ODC and TPK activities were significantly suppressed by dietary DFMO progressively at all stages of colon carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of chemopreventive agents on intermediate biomarkers during different stages of azoxymethane-induced colon carcinogenesis. 130 73

Protein kinase N (PKN) is a soluble, apparently novel serine protein kinase that is activated by nerve growth factor (NGF) and other agents in PC12 pheochromocytoma cells as well as in several nonneuronal cell lines. Purine analogs, such as 6-thioguanine and 2-aminopurine, have been found to inhibit PKN in vitro. When applied to intact cells, these compounds suppress certain biological responses to NGF, but not others, a findings suggesting the presence of multiple pathways in the NGF mechanism. We report here that 6-methylmercaptopurine riboside (6-MMPR) inhibits NGF-stimulated PKN activity in vitro with an apparent Ki of approximately 5 nM. This is approximately 1,000-fold lower than the Ki of the most potent purine inhibitor of PKN. Compounds similar to 6-MMPR, but lacking the methyl or riboside groups, were much less potent as PKN inhibitors. A survey of six additional purified protein kinases shows no inhibitory effect of 6-MMPR, thus indicating a good degree of specificity of this compound for PKN. In contrast to NGF-stimulated PKN, a PKN-like activity stimulated in PC12 cells in response to activation of cyclic AMP-dependent protein kinase was nearly insensitive to 6-MMPR. Application of 6-MMPR to intact PC12 cells resulted in blockade of several responses to NGF (neurite regeneration and ornithine decarboxylase induction) but not of several others (rapid enhancement of tyrosine hydroxylase phosphorylation and PKN activation). These findings suggest that 6-MMPR is a potent and selective agent for characterizing PKN in vitro and for assessing its potential role in the multiple pathways of the NGF mechanism of action.
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PMID:6-Methylmercaptopurine riboside is a potent and selective inhibitor of nerve growth factor-activated protein kinase N. 130 69

In the present study the involvement of protein kinase-C (PKC) in the regulation of the vitamin D receptor (VDR) and interaction of PKC with cAMP-induced up-regulation of VDR in osteoblast-like cells were examined. Activation of PKC by incubation for 4 h with the phorbol ester phorbol 12-myristate 13-acetate (PMA) resulted in a comparable dose-dependent decrease in 1,25-dihydroxyvitamin D3 binding in the osteoblast-like cell lines UMR 106 and ROS 17/2.8, with a maximum inhibition at 100 nM and an IC50 at 5 nM PMA. Time-course studies revealed that in both UMR 106 and ROS 17/2.8 cells, 24-h incubation with PMA caused an increase in 1,25-dihydroxyvitamin D3 binding. This can be related to down-regulation of PKC. Scatchard analysis demonstrated that activation of PKC resulted not in a change in receptor affinity, but, rather, in an increase in VDR number. This is supported by Northern blot analysis, which shows at 2 h a decrease and at 24 h an increase in VDR mRNA. At 4 h, when activation of the cAMP pathway results in an increase in VDR, activation of PKC results in a decrease in VDR. Coincubation for 4 h with PMA caused a decrease in PTH- and forskolin-induced up-regulation of VDR. This inhibition is not due to a reduction in cAMP production, as PTH-stimulated cAMP production was potentiated by PMA. The effect of activation of PKC on VDR is not a general effect, as PMA does not affect basal ornithine decarboxylase activity and potentiates PTH-induced ornithine decarboxylase activity. The present study demonstrates that PKC is involved in the regulation of VDR in UMR 106 and ROS 17/2.8 and that PKC interacts with cAMP in the regulation of VDR. The current data point to a negative controlling role for PKC in the regulation of VDR. Moreover, two different cAMP-regulated actions in UMR 106 cells (VDR up-regulation and ornithine decarboxylase activity) are differently modulated by PKC. Although the precise mechanism by which PKC represses and stimulates gene expression is not yet clear, this study demonstrates the important regulatory role for PKC in two osteoblast-like sarcoma cell lines.
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PMID:Bidirectional regulation of the 1,25-dihydroxyvitamin D3 receptor by phorbol ester-activated protein kinase-C in osteoblast-like cells: interaction with adenosine 3',5'-monophosphate-induced up-regulation of the 1,25-dihydroxyvitamin D3 receptor. 131 52

Parathyroid hormone (PTH) has been shown to induce osteoblastic activity via a complex signal transduction process which is mediated either by cAMP or cytosolic calcium ([Ca2+]i), or a combination thereof. One of the PTH functions in osteoblasts is the induction of ornithine decarboxylase (ODC) activity. We have analyzed the second messengers involved in this process. 8-Bromo cAMP, a cAMP derivative, enhanced ODC activity in UMR106-01 osteoblastic cell system. The calcium ionophore A23187 and the protein kinase stimulator phorbol-12-myristate 13-acetate did not alter ODC activity. ODC activity was increased by bPTH-(1-34), PGE1, and PGE2 which stimulated both cAMP and [Ca2+]i. In contrast, PTH-(2-34), propionyl bPTH-(2-34), bPTH-(3-34), bPTH-(7-34), and PGF2 alpha, which only enhanced [Ca2+]i but not cAMP, had no effect on ODC activity. Thus, the stimulation of ODC in UMR106 cells by PTH appeared to be mediated primarily via the cAMP signal transduction pathway, and the mere increase in intracellular calcium could not account for the stimulation of ODC activity. ODC mRNA level was found to be increased by PTH treatment. Therefore, translation of ODC may be stimulated by PTH. Moreover, PTH also stimulated ODC antizyme activity, suggesting that the ODC degradation rate was increased.
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PMID:Regulation of ornithine decarboxylase by parathyroid hormone in osteoblastic cell systems. 133 75


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