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)

We investigated the relation between cyclic AMP (cAMP) and nitric oxide (NO) production, as well as the effect of NO on Na , K+-ATPase activity in the human neuroblastoma cell line SH-SY5Y. Two cAMP agonists, dibutyryl cAMP (DBC) and beraprost sodium (BPS), increased cAMP accumulation and NO production in a time and dose dependent manner at 50 mmol/l glucose. On the other hand, cellular sorbitol and myo-inositol contents and protein kinase C activity were not altered by DBC or BPS. A specific protein kinase A inhibitor, H-89, suppressed increases in nitrite/nitrate and cyclic GMP (cGMP) and protein kinase A activity stimulated by DBC or BPS. This finding suggests that cAMP stimulates NO production by activating protein kinase A via a pathway different from the sorbitol-myo-inositol-protein kinase C pathway. We observed that an NO donor, sodium nitroprusside, and an NO agonist, L-arginine, enhanced ouabain sensitive Na+, K+-ATPase activity at 50 mmol/l glucose. We also found that a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), inhibited Na+, K+-ATPase activity at 5 mmol/l glucose, and partially suppressed the enzyme activity stimulated by DBC or BPS. The results of this study suggest that cAMP regulates protein kinase A activity, NO production and ouabain sensitive Na+, K+-ATPase activity in a cascade fashion. The results also suggest that protein kinase A at least partially regulates Na+, K+-ATPase activity without mediation by NO in SH-SY5Y cells. We speculate that cAMP and NO are two important regulatory factors in the pathogenesis of diabetic neuropathy.
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PMID:cAMP regulates nitric oxide production and ouabain sensitive Na+, K+-ATPase activity in SH-SY5Y human neuroblastoma cells. 986 12

Cardiac sarcoplasmic reticulum (SR) membrane contains several chloride (Cl-) channels. We have characterized a 116-pS Cl- channel (500 mM cis, 50 mM trans Cl-) in cardiac SR that is activated by protein kinase A-dependent phosphorylation. To understand its function further, we examined the permeation of various anions and adenine nucleotides using the planar lipid bilayer-vesicle fusion technique. This Cl- channel showed a high selectivity to anions and its permeability sequence was Br- > Cl- > I- > NO3- > F-. When all anions were replaced with ATP in the cis solution, channel activity persisted. The conductance was 78 pS with 200 mM ATP and 68 pS with 100 mM ATP. The reversal potentials were +63 mV and +41 mV in 200 mM ATP and in 100 mM ATP, respectively. With 100 mM ADP or AMP in the cis solution, channel activities were also observed. The conductances were 87 pS with 100 mM ADP and 115 pS with 100 mM AMP. The apparent adenine selectivity of this channel was ATP > ADP > AMP, assuming that they exist as divalent anions. These results suggest that the SR Cl- channel in cardiac cells may serve as a transporter for the movement of adenine nucleotides between cytosol and SR lumen.
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PMID:Anion permeability and conduction of adenine nucleotides through a chloride channel in cardiac sarcoplasmic reticulum. 989 Sep 68

Tumor necrosis factor (TNF)-alpha, a pluripotent cytokine implicated in the pathogenesis of airway inflammation, has been shown to provoke hypersecretion of mucin by airway epithelial cells in vitro. In this study, we investigated potential signaling pathways mediating TNF-alpha-induced mucin secretion using guinea pig tracheal epithelial (GPTE) cells in air-liquid interface culture. Exogenously applied TNF-alpha (human recombinant) stimulated mucin secretion in a concentration-dependent manner, with maximal effects at 10 to 15 ng/ml (286 to 429 U/ml). The pathway of stimulated secretion appeared to involve generation of intracellular nitric oxide (NO), activation of soluble guanylate cyclase (GC-S), production of cyclic guanosine monophosphate (cGMP), and activation of cGMP-dependent protein kinase (PKG). TNF-alpha increased production of nitrite and nitrate by GPTE cells; both mucin secretion and cGMP production were attenuated by NG-monomethyl-L-arginine (1 mM), a competitive inhibitor of nitric oxide synthase (NOS), or by the GC-S inhibitor LY83583 (50 microM); and mucin secretion in response to TNF-alpha or to the cGMP analogue dibutyryl cGMP (100 and 500 microM) was attenuated by the specific PKG inhibitor KT5823 (1 microM). Increased mucin secretion and increased cGMP production in response to TNF-alpha both appeared to be mediated by a phospholipase C that hydrolyzes phosphatidylcholine (PC-PLC), and by protein kinase C (PKC), since both responses were attenuated by either D609 (10 and 20 microg/ml), a specific PC-PLC inhibitor, or by each of three PKC inhibitors: Calphostin C (0.3 and 0.5 microM), bisindoylmaleimide (GF 109203X, Go 6850; 20 nM), or Ro31-8220 (10 microM). Collectively, the results suggest that TNF-alpha stimulates secretion of mucin by GPTE cells via a mechanism(s) dependent on PC-PLC and PKC, and involving activation of NOS, generation of NO, production of cGMP, and activation of PKG.
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PMID:Tumor necrosis factor-alpha stimulates mucin secretion and cyclic GMP production by guinea pig tracheal epithelial cells in vitro. 1003 Aug 39

The effects in bovine coronary arteries of the soluble guanylyl cyclase inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) were examined in order to establish the relative importance of the enzyme (a) in the vasodilator actions of glyceryl trinitrate and S-nitroso-N-acetylpenicillamine and (b) in induction of tolerance to these agents. ODQ strongly inhibited responses to both relaxants with IC50's of the order of 0.5 microM; in contrast, the protein kinase G inhibitor, 8-bromoguanosine-3',5'-monophosphorothioate (Rp-8-Br-cGMPS) had little effect on the responses. Tolerance after pre-incubation with glyceryl trinitrate (10 microM) was unaffected by co-pre-incubation with ODQ (1.0 microM), but similar experiments with S-nitroso-N-acetylpenicillamine were inconclusive because tolerance was associated with depressed contractile activity. It is concluded that in bovine coronary arteries soluble guanylyl cyclase is essential for vasorelaxation to both glyceryl trinitrate and S-nitroso-N-acetylpenicillamine but is unimportant for induction of tolerance to glyceryl trinitrate. Our results add weight to the hypothesis of impaired biotransformation rather than guanylyl cyclase desensitisation as the mechanism of in vitro nitrate tolerance.
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PMID:Effects of guanylyl cyclase and protein kinase G inhibitors on vasodilatation in non-tolerant and tolerant bovine coronary arteries. 1032 78

The involvement of adenylate cyclase-cyclic adenosine monophosphate (AC-cAMP) in gonadotropin-stimulated testicular steroidogenesis is well known. Little is known about the role of guanylate cyclase-cyclic guanosine monophosphate (GC-cGMP) or early chloride conductance stimulated by gonadotropins in steroidogenesis. Human chorionic gonadotropin (hCG) 1 IU/L caused significant androgen secretion without a discernible effect on cAMP production. Despite negligible intracellular cAMP, the protein kinase A inhibitor H89 blocked basal and hCG-stimulated steroidogenesis. The GC inhibitors methylene blue (MB) and LY83583 decreased androgen secretion, but hCG did not stimulate cGMP production and there was not a steroidogenic response to exogenous cGMP. A chloride-channel inhibitor, diphenylamine-2-carboxylate (DPC), at concentrations up to 0.6 mmol/L stimulated basal steroid secretion and hCG 10 IU/L stimulated cAMP production, but higher concentrations had an inhibitory effect. Substitution of chloride by gluconate enhanced basal steroid secretion, but nitrate completely abolished the effect of 1 IU/L hCG on androgen secretion, which could be partially overcome by increasing the gonadotropin concentration. In conclusion, chloride, perhaps by activating AC-cAMP, mediates the steroidogenic action of gonadotropins in mouse Leydig tumor cells (MLTC-1). Inorganic nitrate probably inhibited steroidogenesis via conversion to nitric oxide (NO) without involving the GC-cGMP pathway. Nevertheless, the results obtained with GC inhibitors suggest a role for the GC-cGMP pathway in Leydig cell steroidogenesis.
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PMID:Role of chloride and inhibitory action of inorganic nitrate on gonadotropin-stimulated steroidogenesis in mouse Leydig tumor cells. 1038 Nov 42

His-Asp phosphorelay systems have been recently discovered in plants and have emerged as some of the most important signaling systems. The phosphorelay systems in plants include components with sensor (His-protein kinase) domains, His-containing phosphotransfer (HPt) domains, and receiver (response regulator) domains. Recent studies implicate phosphorelay systems in sensing and propagating signals from a wide variety of external and/or internal stimuli such as ethylene, cytokinin, and osmolarity. In maize and Arabidopsis, some response regulators are up-regulated by both cytokinins and nitrate. These findings imply that the His-Asp phosphorelay may operate in an inorganic nitrogen-signaling pathway mediated by cytokinin in plants.
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PMID:His-Asp phosphorelay signaling: a communication avenue between plants and their environment. 1079 27

Blue light-induced oxygen uptake of the colorless mutant of Chlorella kessleri (No. 9.80) was 30-40% higher in the presence of exogenous glycine than in its absence. None of the other amino acids tested had this effect. Moreover, mutant cells in which glutamine synthetase was inhibited by methionine sulphoximine, accumulated approximately 65% more ammonium ions under blue irradiation in the presence of exogenous glycine than in its absence. The protein kinase C inhibitors, staurosporine or K252a, reduced the enhancement of oxygen uptake by approximately 40%. The present results indicate that blue light-dependent deamination of endogenous glycine might be a prerequisite for enhanced oxygen uptake in Chlorella. This blue light-induced oxygen uptake was not influenced by the inhibitors of protein phosphatase, calyculin A or okadaic acid. On the contrary, calyculin A and okadaic acid had a marked effect on the acidification of the suspension medium and nitrate uptake induced by blue light in Chlorella cells. The different responses to the inhibitors of protein kinase and phosphatase suggest the presence of different pathways among the blue light signal transduction operating on oxygen uptake, acidification of the medium and nitrate uptake in Chlorella.
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PMID:Oxygen uptake, acidification of medium and nitrate uptake induced by blue light in nitrate-starved Chlorella cells. 1084 68

NO, constitutively produced by endothelial NO synthase (eNOS), plays a key regulatory role in vascular wall homeostasis. We generated transgenic (Tg) mice overexpressing eNOS in the endothelium and reported the presence of reduced NO-elicited relaxation. The purpose of this study was to clarify mechanisms of the reduced response to NO-mediated vasodilators in eNOS-Tg mice. Thoracic aortas of Tg and control mice were surgically isolated for vasomotor studies. Relaxations to acetylcholine and sodium nitroprusside were significantly reduced in Tg vessels compared with control vessels. Relaxations to atrial natriuretic peptide and 8-bromo-cGMP were also significantly reduced in Tg vessels. Reduced relaxations to these agents were restored by chronic N(G)-nitro-L-arginine methyl ester treatment. Basal cGMP levels of aortas were higher in Tg mice than in control mice, whereas soluble guanylate cyclase (sGC) activity in Tg vessels was approximately 50% of the activity in control vessels. Moreover, cGMP-dependent protein kinase (PKG) protein levels and PKG enzyme activity were decreased in Tg vessels. These observations indicate that chronic overexpression of eNOS in the endothelium resulted in resistance to the NO/cGMP-mediated vasodilators and that at least 2 distinct mechanisms might be involved: one is reduced sGC activity, and the other is a decrease in PKG protein levels. We reported for the first time that increased NO release from the endothelium reduces sGC and PKG activity in mice. These data may provide a new insight into the mechanisms of nitrate tolerance and cross tolerance to nitrovasodilators.
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PMID:Mechanisms of reduced nitric oxide/cGMP-mediated vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase. 1090 19

We investigated the effects of nicorandil, which is a hybrid between a nitrate and an ATP-sensitive potassium channel (K(ATP)) opener, on cultured rat mesangial cell proliferation. Nicorandil (1 microM to 1 mM inhibited [(3)H]thymidine incorporation into rat mesangial cells in a concentration-dependent manner. Nicorandil (1 microM to 1 mM) also inhibited the number of cells. Nicorandil increased cyclic guanosine 3',5'-cyclic monophosphate accumulation in mesangial cells. A protein kinase G inhibitor, KT5823, partially eliminated the inhibition of mesangial cell proliferation by nicorandil. Methylene blue, a guanylate cyclase inhibitor, blocked the inhibitory effect of nicorandil on mesangial cell proliferation. We also examined the effects of K(ATP) mediators. Cromakalim, a K(ATP) activator, and glibenclamide, a K(ATP) inhibitor, had little effect on the proliferation of mesangial cells. These results suggest that the inhibitory effects of nicorandil on mesangial cell proliferation are mediated via the protein kinase G pathway.
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PMID:Inhibitory effects of nicorandil on rat mesangial cell proliferation via the protein kinase G pathway. 1128 62

This review highlights progress in dissecting how plant nitrate reductase (NR) activity is regulated by Ca2+, protein kinases, protein kinase kinases, protein phosphatases, 14-3-3 proteins and protease(s). The signalling components that regulate NR have also been discovered to target other enzymes of metabolism, vesicle trafficking and cellular signalling. Extracellular sugars exert a major impact on the 14-3-3-binding status and stability of many target proteins, including NR in plants, whereas other stimuli affect the regulation of some targets and not others. We thus begin to see how selective or global switches in cellular behaviour are triggered by regulatory networks in response to different environmental stimuli. Surprisingly, the question of how changes in NR activity actually affect the rate of nitrate assimilation is turning out to be a tough problem.
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PMID:Regulation of plant NR activity by reversible phosphorylation, 14-3-3 proteins and proteolysis. 1128 2


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