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)

Dibutyryl cyclic AMP (dB-cAMP) elicits a concentration-dependent stimulation of tyrosine hydroxylase activity in the striatal and mesolimbic synaptosomes. The per cent of stimulation is significantly higher in the mesolimbic synaptosomes than in the striatal synaptosomes. dB-cAMP and depolarizing agents (ouabain or veratridine) have an additive effect on synaptosomal tyrosine hydroxylase activity, indicating that they stimulate tyrosine hydroxylase activity by different mechanisms. cAMP does not stimulate soluble striatal tyrosine hydroxylase activity unless it is added in combination with ATP and Mg2+, compounds required for the activity of cAMP-dependent protein kinase. The cAMP elicited per cent stimulation of soluble tyrosine hydroxylase activity is dependent upon the concentration of added protein kinase and upon the pH of the reaction. dB-cAMP has the same effect on the kinetic state of tyrosine hydroxylase in synaptosomes as cAMP on the soluble tyrosine hydroxylase. The nucleotide does not alter the apparent Km for tyrosine, reduces the Km for the pteridine cofactor and increases the Ki for dopamine. Thus, cAMP increases the affinity of tyrosine hydroxylase for the pteridine cofactor and concomitantly decreases the affinity for the end-product inhibition.
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PMID:Stimulation of tyrosine hydroxylase activity by cyclic AMP in synaptosomes and in soluble striatal enzyme preparations. 0 24

An apparent enigma during platelet aggregation is that increased glycogenolysis occurs despite a fall in cyclic AMP levels; Activation by a classical cascade is therefore unlikely, and an alternative stimulus for phosphorylase a formation was sought. It was found that low levels of Ca-2+ markedly activate phosphorylase b kinase from human platelets, with a Ka of 0i muM Ca-2+, which is similar to that for the skeletal muscle enzyme; The kinase activity is unstable, and on enzyme ageing is a 50% loss in activity with the Ka decreasing to 0.33 muM Ca-2+. In unstilulated platelets, phosphorylase a was 13.3% of toal measured activity, and glycogen synthetase I was 32.3%. Aggregation induced by ADP did not change the percentage of I synthetase, while increasing that for phosphorylase a. Dibutyryl cyclic AMP did, as expected, increase the percentage of both phosphorylated enzymes; These findings suggest that the natural activator of platelet glycogenolysis during aggregation is Ca-2+, which directly stimulates phosphorylase b kinase without altering glycogen synthetase activity. The cyclic AMP-dependent protein kinase does not appear to be involved;
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PMID:Control of platelet glycogenolysis; Activation of phosphorylase kinase by calcium. 16 52

Dibutyryl cyclic AMP and theophylline kill S49.1 mouse lymphoma tissue culture cells. When cells are grown in soft agar with these drugs, the few clones that survive are resistant to cytolysis. The rate of mutation to resistance is 1-3 times 10-7/cell/generation in both diploid and tetraploid cells. The incidence of mutants is increased by treatment with a chemical mutagen, ICR 191. The mutation is consistently associated with greatly reduced or absent cytoplasmic cyclic AMP binding protein. These results suggest that a somatic mutation leads to a defect of the protein kinase regulatory subunit and that activity of this kinase is required for induction of cell death by cyclic AMP.
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PMID:Somatic genetic analysis of cyclic AMP action: selection of unresponsive mutants. 16 36

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

1. The effects of thyroliberin were studied in cultured rat pituitary-tumour cells that synthesize and secrete prolactin (the GH4C1 cell strain). 2. Prolactin and cyclic AMP were measured by radioimmunological methods, and a cyclic AMP-dependent protein kinase was characterized by using histone as substrate. 3. Prolactin release was studied after 5-60min of treatment, and synthesis after 48h of treatment with thyroliberin. One-half maximum stimulation of release and synthesis were observed at 0.25 and at 4nM respectively. 4. Cyclic AMP was temporarily increased in cell suspensions after treatment with thyroliberin, and one-half maximum stimulation was observed at 25nM. 5. Dibutyryl cyclic AMP increased prolactin release and synthesis, one-half maximum effects being obtained at 20 micronM. 6. A cyclic AMP-dependent protein kinase, which was one-half maximally stimulated at 30 nM-cyclic AMP, was demonstrated. 7. An increase in the activity ratio (-cyclic AMP/+cyclic AMP) of the cyclic AMP-dependent protein kinase was observed after treatment with thyroliberin. Total protein kinase activity in the presence of cyclic AMP was unaltered. The time-course of enzyme activation was similar to that of cyclic AMP formation and corresponded to the time when prolactin release was first observed. 8. It is concluded that thyroliberin induces cyclic AMP formation, resulting in the activation of a cyclic AMP-dependent protein kinase.
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PMID:Effect of thyroliberin on the concentration of adenosine 3':5'-phosphate and on the activity of adenosine 3':5'-phosphate-dependent protein kinase in prolactin-producing cells in culture. 19 21

32P phosphorylation of plasma membranes from human blood platelets, under conditions that closely resemble physiological ones (endogeneous phosphate donors and intact platelets in homologous plasma), result in the incorporation of the label mainly in a membrane glycoprotein of apparently high molecular weight (greater than 400 000). Dibutyryl cyclic AMP, an inhibitor of platelet aggregation, specifically increases the degree of phosphorylation of this glycoprotein. Moreover, it has been found that prostaglandin E1 one of the most potent inhibitors of platelet aggregation which also increases phosphorylation of the same glycoprotein, is significantly more effective than cyclic AMP. Cyclic GMP does not have any apparent effect on platelet aggregation. However, incubation of platelet-rich plasma with both cyclic GMP and cyclic AMP results in a partial recovery of the platelet responsiveness towards ADP-induced aggregation. Coincidently, the degree of phosphorylation of the high molecular weight glycoprotein under these conditions, although still higher than in controls (no nucleotides added), is significantly decreased as compared with cyclic AMP-treated cells. Furthermore, cyclic GMP inhibits the cyclic AMP-dependent protein kinase activity in isolated platelet plasma membranes. These results suggest a central role for this membrane phosphoglycoprotein in the triggering of platelet aggregation and, furthermore, suggest that modulation of its degree of phosphorylation may be exerted through some cyclic AMP/cyclic GMP relationship, which in the basal state might be critical for platelet responsiveness.
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PMID:Modulation of platelet responsiveness through selective phosphorylation of plasma membrane proteins. 21 26

Metabolism of dibutyryl cyclic AMP was studied by including the 3H- or C-labeled nucleotide (0.1 mM, 5 mumol) in the recirculating perfusate of the isolated rat kidney. Kidneys were perfused with nucleotide for 60 min. Dibutyryl cyclic AMP was almost completely cleared from the perfusate, about one-quarter as urinary excretion principally by probenecid-sensitive secretion and about one-half as metabolism beyond 3'-phosphate bond cleavage. The principal metabolite, N6-monobutyryl adenosine, accounted for one-third of added dibutyryl cyclic AMP. The remaining metabolites were ATP, ADP AMP, and N6-monobutyryl AMP. Dibutyryl cyclic AMP (0.1 or 1.0 mM) elevated renal ATP but did not alter uricogenesis. Both dibutyryl cyclic AMP and cyclic AMP at 0.2 mM produced similar activation and subcellular redistribution of renal protein kinase. N6-monobutyryl adenosine, unlike adenosine, had no effect on the renal activity of adenylate cyclase, low Km cyclic AMP phosphodiesterase, and protein kinase. Dibutyryl cyclic AMP is like exogenous cyclic AMP in that it penetrates the rat kidney, activates protein kinase, and is metabolized to ATP (R. Coulson, J. Biol. Chem. 251: 4958-4967, 1976), but is unlike cyclic AMP in its extent of secretion and metabolism to ATP and urate and in its formation of the unique metabolites N6-monobutyryl AMP and N6-monobutyryl adenosine.
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PMID:Renal metabolism of N6,O2'-dibutyryl adenosine 3',5'-monophosphate. 22 50

The hypothalamus has the highest concentration of proglucagon-derived peptides (Pgdp's) in the brain, however, the control of the synthesis and secretion of these peptides is not understood. The goal of our studies was to examine in detail the regulation of synthesis and secretion of Pgdp's in the hypothalamus. Hypothalamic cultures were prepared from fetal rats on day 19-21 of gestation and Pgdp's in media and cells were determined by radioimmunoassay after treatment with test agents. Dibutyryl cyclic AMP or forskolin, activators of protein kinase A, markedly stimulated both Pgdp synthesis (by 5-fold) and secretion (by 10-fold) after 24 h of treatment (p < 0.05). The effects of protein kinase A stimulation on Pgdp's in the hypothalamus were greater than seen in our previous studies with the Pgdp-producing pancreatic A and intestinal L cells. Therefore there are tissue-specific differences with regard to the magnitude of the response of Pgdp's to protein kinase A stimulation. Consistent with an involvement of protein kinase A in hypothalamic Pgdp synthesis and secretion, somatostatin-14, an inhibitor of protein kinase A, was found to inhibit Pgdp synthesis and secretion in a dose-dependent fashion (p < 0.05). Phorbol myristate acetate (PMA), a stimulator of protein kinase C, did not significantly affect the synthesis or secretion of Pgdp's at 6 h, but significantly stimulated Pgdp secretion after 24 h (p < 0.05). The inactive phorbol ester, phorbol triacetate was without effect on Pgdp synthesis or secretion after 24 h of incubation (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Control of proglucagon-derived peptide synthesis and secretion in fetal rat hypothalamus. 133 38

During acid secretion, gastric parietal cells undergo profound morphological changes including formation of the apical secretory membrane. To examine the mechanism of histamine-induced increases in the apical membrane area at the single cell level, we monitored the membrane capacitance by applying a time-resolved phase-sensitive detection method to singly isolated parietal cells of guinea pig. A real-time increase in the membrane capacitance was detected within several min after stimulation with histamine. An H2-blocker (cimetidine), but not an H1-blocker (pyrilamine), inhibited the histamine response. Dibutyryl cyclic AMP mimicked the histamine effect. The capacitance response to histamine was sensitive to cytosolic Ca2+, temperature and N-ethylmaleimide. The histamine response was inhibited by intracellular application of a non-hydrolyzable ATP analog (AMP-PNP) and an isoquinolinesulfonamide derivative that works as an inhibitor of protein kinase A (H-8). These results indicate that in parietal cells, elevation of intracellular cyclic AMP induces exocytotic insertion of intracellular membranes into the plasma membrane, presumably by activating protein kinase A.
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PMID:Membrane capacitance increases induced by histamine and cyclic AMP in single gastric acid-secreting cells of the guinea pig. 133 79

Glucocorticoids stimulate the prostaglandin E2 production of confluent amnion cell cultures, but have no stimulatory effect on the PGE2 output of freshly isolated human amnion cells. Since protein phosphorylation may modify the responsiveness of target cells to steroids, and activators of protein kinase C (PKC), as well as corticosteroids, promote amnion cell PGE2 output by stimulating the synthesis of prostaglandin endoperoxide H synthase (PGHS), we investigated the possibility that PKC is involved in the glucocorticoid-induction of PGE2 synthesis in cultured amnion cells. The dexamethasone-induced PGE2 output of arachidonate-stimulated cells was blocked by the protein kinase inhibitors staurosporine, K-252a, H7, HA1004, and sphinganine, in a manner consistent with their effect on PKC. However, dexamethasone increased the PGE2 production of cultures treated with maximally effective concentrations of the PKC-activator compound TPA. Moreover, dexamethasone stimulated PGE2 synthesis in cultures which were desensitized to TPA-stimulation by prolonged phorbol ester treatment. Concentration-dependence studies showed that staurosporine completely (greater than 95%) blocked glucocorticoid-provoked PGE2 synthesis at concentrations which did not inhibit TPA-stimulated prostaglandin output, and that K-252a inhibited the effect of TPA by more than 95% at concentrations which decreased the effect of dexamethasone only moderately (approximately 40%). Dibutyryl cyclic AMP had no influence on the basal- or dexamethasone-stimulated PGE2 production, and on the staurosporine inhibition of the steroid effect. These results show that glucocorticoids and phorbol esters control amnion PGE2 production by separate regulatory mechanisms. It is suggested that the response of human amnion cells to glucocorticoids is modulated by protein kinase(s) other than phorbol ester-sensitive PKC and cyclic AMP-dependent protein kinase.
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PMID:Glucocorticoid stimulation of amnion cell prostaglandin synthesis: suppression by protein kinase C inhibitors and independence of phorbol ester-sensitive protein kinase C. 150 1


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