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 separate fourth intracellular microelectrode was used for controlling the conditions of cyclic nucleotide injection in neurons of Helix pomatia. Ionoforetic increase in intracellular cyclic AMP concentration elicits membrane depolarization in many neurons. Phosphodiesterase inhibitors 3-isobutyl-1-methylxantine and SQ-20009 prolong this depolarization and raise its level. In cell F-1 of helix brain sometimes cAMP induces weak hyperpolarization, but this response turns to usual depolarization after 3-isobutyl-1-methylxantine application. It is suggested that cell molecular computer has an analog input, where diffusion of cAMP, cGMP and Ca++ being a modelling process. Adenylate cyclase and guanylate cyclase and ionic channels of membrane are regulated sources. Phosphodiesterases with Ca2+-binding activator proteins are molecular out flowers and protein kinases--detectors that transform the data about the concentrations of cAMP and cGMP into codes for MCC. Protein kinases control over the activity of proteins directly. The depolarization effect on neuron membrane seems to be associated with protein kinase activation or with direct action of cAMP on phospholipase.
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PMID:[Neuron membrane depolarization under the influence of cyclic-3',5'-adenosine monophosphate and its possible role in the neuronal molecular computer (MC)]. 2 73

Guanylate cyclase, cGMP phosphodiesterase and protein kinase activities were determined in kidneys of developing and adult rats. Guanylate cyclase activities of crude kidney homogenates, 100,000 x g supernatant and pellet of 7- and 21-day-old and adult rats were determined (Table I). In the kidneys of 7-day-old rats activity was 162% of adult controls in the homogenates (P less than .001), 144% in the soluble (P less than .005) and 308% in the particulate fraction (P less than .001). In 3-week-old rats activity was still significantly higher at 144% in the homogenate (P less than 0.02) and at 225% in the particulate (P less than .001). Phosphodiesterase activity for cGMP was 7488 +/- 831 pmol cGMP/mg protein . min in 1-week-old and 7674 +/- 1120 in 3-week-old rats vs. 4042 +/- 122 in the adults (P less than .025) (Table II). Chromatography on Sephadex G-200 showed two peaks of cGMP-stimulatable protein kinase in both the adult and newborn kidney and in addition a minor peak of cGMP-stimulatable kinase in the newborn kidny only (Fig. 2).
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PMID:Increases of guanosine 3',5'-monophosphate-related enzymes in kidneys of developing rats. 2 9

In previous studies, cystic fibrosis (CF) fibroblasts were demonstrated to be resistant to the cytotoxic effects of ouabain, dexamethasone, and the sex hormones, dihydrotestosterone, 17beta-estradiol, and progesterone. We now show that CF fibroblasts also exhibit greatly increased resistance to the cytotoxic effects of exogenous dibutyryl cyclic AMP (cAMP), as well as to isoproterenol and theophylline, drugs which are known to increase endogenous levels of cAMP. CF cells were also shown to have normal amounts of (3H)cAMP binding to protein kinase as well as normal amounts of cAMP-stimulated protein kinase activity. Phosphodiesterase in CF cells was also found to be stimulated by cAMP to the same degree as in normal cells. These findings suggest that there is no detectable protein kinase deficiency in CF cells. cf cells thus appear to be unlike some cAMP-resistant mutants described by others which are defective in protein kinase activity and cAMP regulation of phosphodiesterase levels. The cross-resistance of CF fibroblasts to ouabain, steroid hormones, and cAMP may provide a unique opportunity to study the biochemical events involved in the metabolism of these drugs as well as the basic biochemical defect in a common human genetic disease.
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PMID:Pleiotropic drug resistance in cystic fibrosis fibroblasts: increased resistance to cyclic AMP. 21 May 26

DFMO and IFN have both been shown to suppress the intracellular activity of ornithine decarboxylase in rapidly proliferating tissues. In addition, both agents demonstrate antiproliferative activity against human lymphoblastoid (Daudi) cells in culture. Treatment of log-phase Daudi cells with doses of 6 U/ml of IFN or 1 mM DFMO resulted in a 50% reduction of cell number 72 h after drug addition. Combination of IFN with DFMO against DAUDI cells using the isobologram method showed that the two demonstrate true antiproliferative synergy. Analysis of 2',5'-oligoadenylate synthetase (2,5A) activity in treated cells showed that both IFN alone and IFN/DFMO combination result in equivalent 2,5A induction (1800 mmol/mg/20 h) compared to control (300 mmol/mg/20 h). While 2,5A activity decreased by 50% at 48 h in cells after treatment with IFN alone, the IFN/DFMO combination remained elevated (1700 mmol/mg/20 h). Phosphodiesterase (PdE) activity in these cells showed no substantial changes with IFN, DFMO, or IFN/DFMO treatment over 72 h compared to control values. In contrast, the activity of the 68-kDa interferon induced protein kinase (PK) in IFN/DFMO-treated cells was 1.6-fold greater at 48 and 72 h than that found for IFN alone. These studies demonstrate that the synergistic antiproliferative activity of IFN/DFMO combination may be due, in part, to modification of the activity of IFN-inducible enzymes.
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PMID:Biochemical effects of human alpha interferon in combination with alpha-difluoromethylornithine on human lymphoblastoid (DAUDI) cells in culture. 165 71

Mouse Leydig cell androgen production can be acutely stimulated by atrial natriuretic factor (ANF) via cyclic guanosine 3',5'-monophosphate (cGMP). This stimulation can approach that seen with high concentrations of luteinizing hormone (LH) acting via cyclic adenosine 3',5'-monophosphate (cAMP). To assess the potential for synergistic interaction between LH/cAMP and ANF/cGMP Leydig cells were co-exposed to ANF and LH or ANF/cGMP and site/type-selective cAMP analogues. Co-exposure to 1 nM ANF and 1 ng/ml LH elicited a synergistic increase in androgen production. Both 500 microM 8-bromo-cGMP and ANF (1.0-2.5 nM) synergized with cAMP analogues selective for either of the two major isoenzymes of protein kinase A. Phosphodiesterase (PDE) inhibition was not involved as inclusion of a PDE inhibitor only augmented the response. It appears that ANF/cGMP may interact cooperatively with LH/cAMP in the stimulatory control of androgen production in the mouse Leydig cell and that the site of synergistic interaction may be the activation of the cAMP-dependent protein kinase.
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PMID:Interaction between cyclic nucleotide second messenger systems in murine Leydig cells. 166 54

High-affinity antibodies against calmodulin (CaM)-dependent cyclic nucleotide phosphodiesterase and protein phosphatase (calcineurin) were purified and characterized. Rabbit anti-phosphodiesterase antibody did not react with other phosphodiesterases or with the regulatory subunits of cAMP-dependent protein kinase. Affinity-purified goat anti-calcineurin antibody recognized both the 61-kDa catalytic subunit and the 18-kDa Ca2+-binding subunit of the phosphatase. Neither antibody reacted with CaM, several CaM-binding proteins (calmodulin-dependent protein kinase, myosin light chain kinase, fodrin), or other cytosolic proteins from brain. The antibodies were used to compare the cellular localization of these two CaM-dependent enzymes in rat brain. Both calcineurin and phosphodiesterase were found predominantly in nerve cells; however, phosphodiesterase was restricted to very specific neuronal populations. Phosphodiesterase was prominent in the somatic cytoplasm and dendrites of regional output neurons--e.g., cerebellar Purkinje cells and hippocampal and cortical pyramidal cells. The extensive and uniform staining in the dendrites was consistent with postsynaptic localization and suggested an important function for this enzyme in neurons that integrate multiple convergent inputs. Calcineurin was present in virtually all classes of neurons, with immunoreactivity confined primarily to cell bodies. Both diffuse cytoplasmic staining and characteristic punctate staining of cell bodies were observed; the latter suggested compartmentalization of calcineurin at or near the plasma membrane. The results of this study demonstrate that calcineurin and phosphodiesterase are differentially localized in the central nervous system. Thus, the expression and compartmentalization of CaM-binding proteins may be highly regulated and specific for particular differentiated nerve cell types.
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PMID:Differential localization of calmodulin-dependent enzymes in rat brain: evidence for selective expression of cyclic nucleotide phosphodiesterase in specific neurons. 302 62

2'-Phosphodiesterase from NIH 3T3 cells was purified about 530-fold. Treatment of the cell lysate with the cAMP-dependent protein kinase causing the 2'-phosphodiesterase inhibition did not result in phosphorylation of the enzyme itself. The kinase was found to phosphorylate a specific 18-kDa protein, the phosphorylated form of this protein being the inhibitor of 2'-phosphodiesterase.
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PMID:Inhibition of 2'-phosphodiesterase by cAMP-dependent protein kinase. Involvement of phosphorylation of protein inhibitor. 609 39

The two-microelectrode voltage-clamp technique was used to monitor K+ channel activity in Xenopus oocyte follicular cells, which are electrically coupled to the oocyte itself by gap junctions. Endogenous vasodilators such as calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), prostaglandin E2 (PGE2) and adenosine activate glibenclamide-ATP-sensitive K+ (KATP) channels in Xenopus oocyte follicular cells. The mechanism of action of CGRP was studied in detail. CGRP effects undergo a rapid desensitization. CGRP acts via CGRPI receptors. Its effects are antagonised by the amino-truncated CGRP analog hCGRP(8-37). The second messenger for CGRP activation of KATP channels is cAMP. Phosphodiesterase inhibition by 3-isobutyl-1-methylxanthine enhances the CGRP response while adenyl cyclase inhibition by either 2',5'-dideoxyadenosine or progesterone nearly completely depresses the CGRP response. Vasoconstrictors such as ACh and angiotensin II also have receptors in follicular cells. ACh strongly inhibits the CGRP activation of K+ channels as it inhibits the activation of KATP channels by P1060, but angiotensin II does not. It is concluded that as in vascular smooth muscle cells, CGRP and probably other hyperpolarizing vasodilators open KATP channels in follicular cells by protein kinase A activation.
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PMID:CGRP-induced activation of KATP channels in follicular Xenopus oocytes. 753 Aug 40

To investigate the role of cAMP-dependent protein kinase (PKA) and cAMP levels in ATP-dependent mitogenesis, Swiss 3T3 cells were transfected with an expression vector coding for (i) a mutated regulatory subunit of PKA (PKA mutant) or (ii) a yeast low Km cAMP phosphodiesterase gene (PDE mutant). The PKA mutant showed 70% reduced PKA activity. Phosphodiesterase activity increased 2.5-fold in the PDE mutant, leading to a great reduction of cAMP levels stimulated by ATP and other cAMP-increasing agents. The mitogenic responses of PKA and PDE mutants to insulin, epidermal growth factor, or 12-O-tetradecanoylphorbol-13-acetate were not significantly changed. However, the further stimulation by ATP, ADP, and adenosine 5'-(beta,gamma-imido)triphosphate in the presence of these growth factors was reduced by > 80%. Mitogenic effect of prostaglandin E2, forskolin, cholera toxin, or adenosine was inhibited in both mutants. The mitogenic stimulation by dibutyryl cAMP, which is resistant to phosphodiesterase, was inhibited in the PKA mutant, but not in the PDE mutant. A partial reduction of platelet-derived growth factor- or bombesin-stimulated mitogenesis, which involves protein kinase C as well as the cAMP signal, was observed in the mutants. These genetic results confirm pharmacological data on the role of PKA and cAMP levels in mitogenesis due to ATP and other growth factors.
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PMID:Role of adenosine 3':5'-monophosphate-dependent protein kinase and cAMP levels in ATP-dependent mitogenesis in Swiss 3T3 cells. 827 49

In vascular smooth muscle cells (VSMCs) of rat tail artery, prostaglandin E2 (PGE2) inhibited a voltage-dependent, delayed rectifier K channel current (Ik). The inhibition was concentration-dependent, via a receptor-mediated mechanism involving the activation of G protein(s) (Ren et al., 1995). In this study, we show that the PGE2-induced inhibition of Ik was mediated by activation of protein kinase A (PKA) and possibly protein kinase C (PKC). Pretreatment of the cells with cyclic adenosine 3',5'-monophosphothioate Rp-isomer (Rp-cAMPs), an inhibitor of adenosine 3', 5'-cAMP-dependent protein kinase (PKA), almost completely abolished the PGE2-induced inhibition. Forskolin, dibutyryl cAMP (Db-cAMP) and cyclic adenosine 3',5'cyclic monophosphothioate Sp-isomer (Sp-cAMPs), activators of adenylate cyclase and PKA, mimicked the effect of PGE2 on Ik. Phosphodiesterase inhibition by 3-isobutyl-1-methylxanthine did not alter the PGE2-induced inhibition of Ik. Moreover, we also found that phorbol myristate acetate (PMA), a PKC activator, significantly suppressed Ik. Both the kinase inhibitor staurosporine and down-regulation of PKC by prolonged exposure of the cells to PMA blocked the PGE2-induced inhibition of Ik, but had no effects on the forskolin, Db-cAMP or SpcAMP-induced effect on Ik. Pretreatment of the cells with Rp-cAMPs only partially diminished the degree of Ik inhibition evoked by PMA. Assay of cAMP content indicated that both PGE2 and PMA induced cAMP accumulation. These results strongly suggest that the modulation of Ik by PGE2 in rat tail artery VSMCs involves signal transduction through both PKA and PKC activation. The activation of PKC may potentiate the cAMP-PKA stimulation, whereas the cAMP-PKA cascade did not seem to affect the PKC pathway. These observations suggest that "cross talk" between the two second-messenger systems is involved in the mechanisms that mediate the effect of PGE2.
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PMID:The actions of prostaglandin E2 on potassium currents in rat tail artery vascular smooth muscle cells: regulation by protein kinase A and protein kinase C. 861 46


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