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

---

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

The extent of activation of rat submandibular protein kinase A (EC 2.7.1.37) isozymes following beta-adrenergic receptor stimulation was determined in vitro using dispersed cells and an 8-N3-[32P]cAMP photoprobe. The half-maximal binding of the photoprobe for microsomal and cytosolic type I and cytosolic type II was 9 nM, 27 nM and 92 nM, respectively. 'Cold trap' studies indicated that 70% of type I protein kinase A was activated following maximal beta-adrenergic receptor stimulation, whereas type II activation was less than 40%. Both cytosolic and microsomal type I activation occurred rapidly following beta-adrenergic receptor stimulation and both remain activated throughout the entire secretory period. Type I inactivation occurred rapidly subsequent to beta-adrenergic receptor blockade. The dose-response relationship for the isotypes following beta-adrenergic receptor activation demonstrated a greater extent of type I activation at submaximal concentrations of agonist. Although protein kinase A may not be the only kinase involved in rat submandibular mucin release, these data add further support to a direct regulatory role for this kinase, with type I having potentially a greater role than type II.
...
PMID:Subcellular distribution and activation of rat submandibular cAMP-dependent protein kinase following beta-adrenergic receptor stimulation. 283 98

The effect of NaF on cAMP accumulation, cAMP-dependent protein kinase activity (cAMP-dPK) ratios and [14C]-glucosamine-labelled mucin release from these isolated cells was investigated. NaF (0.01-5 mM) increased significantly the cellular cAMP concentration and cAMP-dPK activity ratios in a dose- and time-dependent manner. NaF (5.0 mM) increased [14C]-glucosamine-labelled mucin release in a time-dependent manner. Thus the stimulation of prelabelled mucin secretion by NaF is mediated by an increase in the cAMP concentration, which exerts its effect, at least partly, via the activation of cAMP-dPK activity.
...
PMID:Stimulation of mucin release from rat submandibular salivary-gland cells by NaF. 284 98

The mechanism of beta-adrenergic regulation of mucin secretion was investigated in cat trachea in vitro. beta-Adrenergic agonists increased the release of [35S]SO4-radiolabeled mucin and mucosa-submucosal adenosine 3',5'-cyclic monophosphate (cAMP) levels in a dose- and time-dependent manner. The relative potencies and efficacies of l-isoproterenol, l-epinephrine, l-norepinephrine, terbutaline, and dobutamine for physiological and biochemical events were similar. The effect of these agonists were blocked by d-l-propranolol. 3-Isobutyl-l-methylxanthine (IBMX) and 8-bromo-cAMP mimicked the effects of the agonists on mucin release. IBMX increased cAMP levels and potentiated the increase in cAMP levels effected by beta-adrenergic agonists. The half-maximal effects of l-isoproterenol on cAMP levels and mucin release were attained at 1.6 and 8.8 min, respectively. Three major mucosa-submucosal proteins of apparent molecular weights of 49,000, 54,000, and 59,000 daltons displayed reduced binding of the photoaffinity label 8-N3-[32P]cAMP when endogenous cAMP levels were increased with l-isoproterenol and/or IBMX. The first two proteins correspond in electrophoretic mobility to the regulatory subunits of type I and type II cAMP-dependent protein kinases, respectively. The 59,000-dalton cAMP binding protein may be the phosphorylated form of the regulatory subunit of type II cAMP-dependent protein kinase. These data are consistent with the hypothesis that beta-adrenergic modulation of tracheal mucin release is mediated by cAMP and suggest that activation of cAMP-dependent protein kinases may be involved in the neurohormonal effects.
...
PMID:Beta-adrenergic modulation of mucin secretion in cat trachea. 613 50

The extent of activation of rat submandibular gland cyclic AMP-dependent protein kinase (EC 2.7.1.37) was determined in vitro using dispersed cells to assess the involvement of this enzyme in submandibular mucin secretion. cAMP-dependent protein kinase activation, as determined by activity ratio method, was markedly increased following beta-adrenergic receptor activation. 0.5 M NaCl was required in the homogenization buffer for stabilization of the hormonally activated cAMP-dependent protein kinase. A role for cAMP-dependent protein kinase activation in regulating mucin secretion was strongly suggested by the following: (1) the kinase activity ratio increased rapidly after beta-adrenergic receptor stimulation; (2) dose-response relationship of the kinase activation following beta-adrenergic receptor activation correlated with isoproterenol induced mucin release; (3) termination of beta-adrenergic mediated mucin secretion caused a rapid decrease in the kinase activity ratio; (4) dibutyryl cyclic AMP stimulation caused an increase in the kinase ratio; whereas (5) pure cholinergic and pure alpha-adrenergic receptor stimulation had no effect on endogenous kinase activity. Although cAMP-dependent protein kinase activation may not be the only regulator of mucin secretion, these data suggest an important regulatory role for this kinase activation during rat submandibular mucin release.
...
PMID:Role of cyclic AMP-dependent protein kinase activation in regulating rat submandibular mucin secretion. 629 86

The regulation of intestinal mucin secretion by cytokines, soluble factors released by mucosal activated immune cells, is so far unknown. The aim of the present study was (1) to investigate the regulatory effects of interferon-gamma on baseline and stimulated mucin secretion elicited by an increase in intracellular cAMP, either a short-term increase (induced by vasoactive intestinal peptide or by forskolin) or a long-term increase (cholera toxin-induced), and (2) to attempt to delineate the site of action of interferon-gamma. The in vitro model used was the human colonic goblet cell line Cl.16E, which has already been shown to respond to physiological secretagogues in terms of mucin secretion. We examined the effects of interferon-gamma 1) on mucin exocytosis, measured as release of [3H]glucosamine-labeled macromolecules trapped at the stacking/running gel interface of polyacrylamide gels, and 2) on mucin biosynthesis, examined at the RNA level using a cDNA probe directed to the MUC2 mucin gene. We demonstrated that, while interferon-gamma did not alter baseline Cl.16E mucin secretion and MUC2 gene expression, it strongly inhibited the protein kinase A-dependent secretory response to VIP, forskolin, or cholera toxin. However, interferon-gamma had no effect on the protein kinase A-dependent MUC2 over-expression induced by cholera toxin. We thus concluded that the target for interferon-gamma inhibition of cAMP-stimulated Cl.16E mucin secretion is distal to protein kinase A and might be a component of the exocytotic machinery. Together, our results establish interferon-gamma as a pharmacologically powerful tool to specifically inhibit stimulated secretory processes without affecting baseline secretion.
...
PMID:Interferon-gamma modulates cAMP-induced mucin exocytosis without affecting mucin gene expression in a human colonic goblet cell line. 751 24

In cystic fibrosis (CF), numerous epithelial cell functions are abnormal, including Cl- conductance, sodium absorption, mucin sulphation and enzyme secretion. Although the CF gene product, the cystic fibrosis transmembrane conductance regulator (CFTR), functions as a small linear Cl- channel, it is difficult to attribute such pleiotropic disease manifestations solely to a defect in Cl- conductance. This has led to speculation that CFTR regulates the activity of other proteins. One possible example is the protein kinase A activation of outward rectifying Cl- channels (ORCC), which is defective in membrane patches excised from CF cells. Whether CFTR regulates the activity of an independent anion channel is debatable, because ORCC occur exclusively in excised membrane patches and could be an excision-induced molecular derivative of CFTR. 'Knockout' mice that lack CFTR provide a means to define the relationship between CFTR and ORCC. Here we report that ORCC are present in CFTR(-/-) mouse nasal epithelial cells and thus cannot be a derivative of the CFTR molecule. Also ORCC were regulated by protein kinase A in membrane patches from normal but not CFTR(-/-) cells. These observations are the first, to our knowledge definitive demonstration that CFTR regulates the activity of another protein.
...
PMID:CFTR and outward rectifying chloride channels are distinct proteins with a regulatory relationship. 768 73

We have investigated the regulation of the intestinal mucin gene MUC2 in HT29 cells. Surprisingly, sodium butyrate, an effective inducer of aspects of colonic cell differentiation in HT29 cells, fails to induce MUC2 during short-term exposure, despite the fact that it has been used to select stably differentiated clones of HT29 that resemble goblet cells and produce mucin. However, 12-O-tetradecanoylphorbol-13-acetate and forskolin, which trigger the protein kinase C- and A-dependent signal transduction pathways, respectively, are potent inducers of MUC2 gene expression. 12-O-Tetradecanoylphorbol-13-acetate and forskolin operate through distinct mechanisms, with the former requiring de novo protein synthesis and the latter not. Experiments using specific protein kinase inhibitors suggest that both inducers operate by triggering their respective signal transduction pathways. Nuclear runoff analyses suggest that post-transcriptional (rather than transcriptional) mechanisms are important in the accumulation of MUC2 mRNA. Finally, we show that in several cell lines from human mucinous tumors, characterized by elevated levels of mucin production, MUC2 expression is very high and constitutive compared to forskolin-treated HT29 cells. Thus, the different regulation of MUC2 in HT29 cells and in mucinous tumor cell lines may reflect molecular pathways that characterize colon carcinomas of different histology and pathology.
...
PMID:Regulated expression of an intestinal mucin gene in HT29 colonic carcinoma cells. 768 47

A series of cAMP analogs that have different specificities for the two different binding sites on the regulatory subunit of type I and type II cAMP-dependent protein kinase (PKA) were used to determine whether selective activation of type I or type II PKA could link either or both isozyme forms of PKA with exocytosis and specific protein phosphorylation in salivary gland cells. Using dispersed rat submandibular or parotid cells, selective activation of either type I or type II resulted in a synergistic response for both rat submandibular mucin and parotid amylase secretion and the phosphorylation of a 26-kDa integral membrane phosphoprotein. These data suggest that the activation of either isozyme of PKA can elicit cellular exocytosis and specific protein phosphorylation in both of these cell types.
...
PMID:Rat submandibular and parotid protein phosphorylation and exocytosis: effect of site-selective cAMP analogs. 769 Jun 3

Short-term treatment of rat submandibular tissues with 10 microM isoproterenol (IPR) resulted in reduction of mucin secretion in response to the agonist during further incubation, and in increases in EC50 values. This IPR-induced reduction of secretion was coupled with selective decreases in the number of beta-adrenoceptors in the tissues and in their affinity for agonists, as assessed by measurement of the specific binding of [3H]dihydroalprenolol. Treatment of the tissues with IPR caused a 30% decrease in IPR-stimulated adenylate cyclase activity and a 25% increase in the GTP binding capacity of inhibitory G proteins (Gi proteins). This IPR treatment triggered a 60% increase in the ability of pertussis toxin (IAP) to catalyze ADP-ribosylation of Gi proteins in the tissue membranes. Enhanced function of stimulatory G proteins (Gs proteins) was observed only during the first incubation of the tissues with IPR. The IAP-catalyzed ADP-ribosylation of Gi proteins in tissues treated with IPR was decreased by prior treatment with cyclic AMP dependent protein kinase, but was increased markedly by prior treatment with alkaline phosphatase. Neither IPR-induced desensitization of protein secretion nor increase in the IAP-catalyzed ADP-ribosylation of Gi proteins was observed in the tissues pretreated with 0.25 microM okadaic acid. These findings suggest that the regulation of Gi protein phosphorylation plays an important role in the IPR-induced heterologous desensitization of mucin secretion from rat submandibular glands.
...
PMID:Mechanism of isoproterenol-induced heterologous desensitization of mucin secretion from rat submandibular glands. Regulation of phosphorylation of Gi proteins controls the cell response to the subsequent stimulation. 769 46

The relationship between the adenosine 3',5'-cyclic monophosphate-mediated protein kinase A (PKA)-dependent stimulatory pathway for mucin secretion and Ca(2+)-mediated and protein kinase C (PKC)-mediated secretion was studied in T84 cells, using the postreceptor secretagogues forskolin, A-23187, and phorbol 12-myristate 13-acetate (PMA), the protein kinase inhibitors staurosporine and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), high- and low-Ca2+ media, and the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Staurosporine (10(-5) M) inhibited both PMA and forskolin at their maximally effective concentrations, whereas H-7 (5 x 10(-5) M) inhibited only PMA. Stimulation of mucin secretion by forskolin (5 x 10(-5) M) was not significantly affected by the reduction of medium Ca2+ to 47 and 129 nM, equivalent to published values for intracellular Ca2+ concentration ([Ca2+]i). Stimulation by forskolin was reduced by preloading cells with BAPTA, but to a much smaller extent than Ca(2+)-dependent stimulation by A-23187. A-23187-mediated mucin secretion from BAPTA-loaded cells was augmented by high doses of forskolin. Similar concentrations of forskolin had no effect on A-23187-stimulated secretion in calcium-replete cells. Our results indicate that forskolin does not stimulate mucin secretion by increasing Ca2+ entry or releasing Ca2+ from intracellular stores. Forskolin can stimulate mucin secretion in a Ca(2+)-independent manner but is apparently inhibited by high levels of intracellular Ca2+ induced by Ca2+ ionophores in 1.0 mM Ca2+ media.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Regulation of mucin secretion in T84 adenocarcinoma cells by forskolin: relationship to Ca2+ and PKC. 817 99


1 2 3 4 5 6 7 8 Next >>

---