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 regulation patterns of gastric acid secretion in rats were investigated. Pentagastrin and histamine stimulate gastric acid secretion, but the inhibitors of DNA-dependent synthesis of RNA and of proteins prevent only the pentagastrin action. It has been found that pentagastrin induces histidine decarboxylase in gastric mucosa, ensuring local accumulation of histamine. The latter activates adenylate cyclase and results in 3',5'-AMP accumulation in gastric tissues. The administration of pentagastrin, histamine or 3',5'-AMP enhances the activity of gastric carbonic anhydrase, the enzyme which takes part in HCl formation. The data suggest that these three compounds act sequentially (pentagastrin leads to histamine leads to3',5'-AMP) and the effect of the last one could be mediated through 3',5'-AMP dependent protein kinase. The experiments in vitro demonstrated that gastric carbonic anhydrase can be separated into two isoenzymes and thephosphorylation of one of them by the 3',5'-AMP dependent protein kinase sharply increases its activity. The findings raise the possibility that histamine and 3',5'-AMP, mediating gastrin action, form together with enzymes (histidine decarboxylase, adenylate cyclase, protein kinase, carbonic anhydrase) a caascade of amplifiers. Autoradiographic studies have shown that [3H]-pentagastrin is not bound by oxyntic cells but adheres preferentially to histamine-producing alpha-like endocrine cells and to the chief cells, while 3H-histamine adheres preferentially to oxyntic and to chief cells. Electron microscopy indicates that only pentagastrin (but not histamine) initiates in alpha-like endocrine cells ultrastructural changes characteristic for induction. Pentagastrin, histamine and 3',5'-AMP administration produces in oxyntic cells ultrastructural changes typical for the secretion processes. These results lead to assumption that pentagastrin (gastrin) induces histidine decarboxylase in alpha-like endocrine cells of gastric glands. Histamine which is secreted enhances adenylate cyclase activity in the neighbouring oxyntic cells where 3',5'-AMP dependent protein kinase activates carbonic anhydrase by means of phosphorylation. These different cells form, probably, a multicellular functional unit for gastric acid secretion.
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PMID:Integration of biochemical functions of different cells of rat gastric mucosa for hydrochloric acid secretion. 18 10

In the preceding paper (Kawai, H. et al. (1992) Biochim. Biophys. Acta 1133, 172-178), we reported that in mastocytoma P-815 cells dexamethasone and 12-O-tetradecanoylphorbol-13-acetate (TPA) synergistically enhanced the de novo synthesis of L-histidine decarboxylase (HDC). Here we found that Ca2+ acted synergistically with cAMP in the induction of HDC mRNA and HDC activity in mastocytoma P-815 cells, and that the mechanism underlying the enzyme induction by Ca2+ plus cAMP was distinguishable from that by dexamethasone plus TPA. Ca2+ ionophore A23187, itself having no significant activity, markedly enhanced the induction of HDC activity by N6,O2'-dibutyryl cAMP (db cAMP) or cAMP-inducible prostaglandins such as PGE1, PGE2 and PGI2 in the presence of the phosphodiesterase inhibitor, Ro201724. However, A23187 had little effect on increases in HDC activity induced by other known stimulants, such as TPA, dexamethasone and sodium butyrate. These results suggest that A23187 has a specific effect on the induction of HDC activity due to an increased level of cAMP. The finding that both A23187 and cAMP enhanced HDC activity suggests that both Ca2+/calmodulin and cyclic nucleotide dependent protein kinase play essential roles in the process of enhancement of HDC activity. To examine this possibility, we studied the effects of W-7, an inhibitor of calmodulin, removal of extracellular Ca2+, and H-8, an inhibitor of cAMP-dependent protein kinase, on the enhancing activity of A23187 plus db cAMP. The enhancement of HDC activity by A23187 plus db cAMP was inhibited by W-7, removal of extracellular Ca2+, and H-8. The increase in HDC activity was due to the de novo synthesis of the enzyme, since it was suppressed by the addition of cycloheximide or actinomycin D, and was well correlated with the marked accumulation of a 2.7 kilobase HDC mRNA. Furthermore, the mechanism underlying the induction of HDC by db cAMP plus A23187 is distinguishable from that in the case of dexamethasone plus TPA, since preexposure to dexamethasone plus TPA for 12 h, for a plateau level to be reached, did not affect the subsequent increase in HDC activity due to db cAMP plus A23187.
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PMID:Synergistic effects of cyclic AMP and Ca2+ ionophore A23187 on de novo synthesis of histidine decarboxylase in mastocytoma P-815 cells. 131 51

In order to analyze the mechanisms by which a single biogenic amine like histamine is capable of inducing a wide variety of both physiologic and pathologic functions in various tissues/cells, histamine responses were dissected in detail from a biochemical and pharmacologic point of view. Histamine is synthesized by multiple isozymes of histidine decarboxylase, and catabolized by either diamine oxidase or histamine-N-methyltransferase. Synthesized intracellular histamine may play a role in cell proliferation, whereas released histamine binds to at least three different histamine-specific receptors, then activates various intracellular components, such as Ca++, cAMP, protein kinase, and ion channels. These second messenger pathways interact differentially with each other in various tissues/cells. Moreover, histamine not only activates its own receptors, but also activates other related receptors such as the serotonin 1c receptor. Therefore, to understand the complex actions of histamine, new approaches should be established, in which multiple phenomena can be monitored simultaneously.
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PMID:Functional diversity of histamine and histamine receptors. 158 29

Conditions favouring protein phosphorylation and dephosphorylation are examined for their effects on activity and charge heterogeneity of the rat gastric mucosal histidine decarboxylase. Incubation of gastric supernatant with various combinations of ATP, Mg2+, cyclic AMP and protein kinase under the blockade of endogenous phosphodiesterase and phosphatase fails to alter significantly enzyme activity as assayed with or without pyridoxal 5'-phosphate. Similar results are found with the purified enzyme. No change occurs in the distribution of activity between the charged forms. In contrast, treatment with alkaline phosphatase both inactivates the enzyme with preservation of heterogeneity, full reactivation being achieved by pyridoxal 5'-phosphate, and reduces the number of forms and converts forms II and III to form I with preservation of the catalytic potentialities. The data suggest that the enzyme heterogeneity may be related in part to the phosphorylation state; the possibility that the gastric enzyme is susceptible to several post-translational modifications is discussed.
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PMID:Relationship between the multiple forms of rat gastric histidine decarboxylase: effects of conditions favouring phosphorylation and dephosphorylation. 215 9

Mouse mastocytoma histidine decarboxylase is decreased in activity when, in crude preparations, incubated with a cAMP-dependent protein kinase. This effect was not seen with purified preparations of the histidine decarboxylase (specific activity 7-13 mumol X mg-1 X h-1). Further, no incorporation of 32P from AT32P during incubation of this enzyme with the protein kinase could be demonstrated. Therefore, if protein phosphorylation operates in the regulation of the histidine decarboxylase, factors removed during the purification must be involved.
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PMID:Mammalian histidine decarboxylase: effect by protein kinase on mouse mastocytoma histidine decarboxylase. 640 11

In this study we investigated the short-term effect of somatostatin on histamine synthesis in a cell population isolated from rabbit gastric mucosa and enriched in enterochromaffin-like cells. Somatostatin inhibited basal and gastrin-stimulated histamine synthesis through a dual mechanism involving a decrease in the affinity of histidine decarboxylase (HDC) for its substrate (L-histidine) and a reduction in the number of functional HDC molecules. H-89 (an inhibitor of cAMP-dependent protein kinase) mimicked somatostatin-induced reduction of HDC affinity, which, on the contrary, was selectively reversed by pertussis toxin (PTX). Furthermore, forskolin was shown to reverse the inhibitory effect of H-89 and to prevent the somatostatin-induced reduction in HDC affinity for L-histidine. Thus, the somatostatin-induced reduction in affinity seems to involve a PTX-sensitive G protein and an inhibition of the cAMP-dependent pathway. On the other hand, the somatostatin-induced decrease in the number of functional HDC molecules seems to be PTX insensitive and independent from a modulation of the cAMP pathway, and does not seem to involve a significant change in HDC messenger RNA expression or a regulation of protein kinase C. The exact nature of this second mechanism will need further studies to be elucidated.
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PMID:Short-term inhibitory effect of somatostatin on gastric histamine synthesis. 904 95

The inflammatory exudate at the post-anaphylaxis phase of allergic inflammation in rats has an ability to enhance histamine production by bone marrow cells. To analyze the mechanism of the inflammatory exudate-induced histamine production pharmacologically, the effects of several drugs were examined in cultures of bone marrow cells. Incubation of the bone marrow cells in the presence of the inflammatory exudate that had been centrifuged and dialyzed against Hanks' balanced salt solution increased histidine decarboxylase activity in the cells and histamine concentration in the conditioned medium. The induction of histamine production by the inflammatory exudate was inhibited by actinomycin D (0.01-1 microM), an inhibitor of RNA synthesis, and cycloheximide (0.1-10 microM), a protein synthesis inhibitor. The protein kinase C inhibitors staurosporine (2-20 nM), K-252a (6-200 nM), and H-7 (10.3-103 microM) also inhibited the inflammatory exudate-induced histamine production in a concentration-dependent manner. The tyrosine kinase inhibitor genistein (3.7-37 microM) also inhibited the inflammatory exudate-induced histamine production, but the protein kinase A inhibitor H-89 (0.2 microM), and the adenylate cyclase activator forskolin (0.1 microM) showed no effect. These findings suggest that histamine production induced by the inflammatory exudate is mediated by the de novo synthesis of histidine decarboxylase and by the activation of protein kinase C and tyrosine kinase.
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PMID:Pharmacological analysis of the inflammatory exudate-induced histamine production in bone marrow cells. 913

Gastrin stimulates transcription of the human histidine decarboxylase (HDC) gene through binding to the G-protein-coupled cholecystokinin-B/gastrin receptor. We have explored the possibility that mitogen-activated protein kinase cascades play a role in mediating the effects of gastrin on transcription in a gastric cancer (AGS-B) cell line. Gastrin and phorbol 12-myristate 13-acetate (PMA) treatment of AGS-B cells was found to increase the phosphorylation of tyrosine residues of extracellular signal-regulated kinases (ERKs) 1 and 2 and increase ERK activity as determined by the in vitro phosphorylation of myelin basic protein. Reporter gene assays also demonstrated that gastrin and PMA stimulated Elk-1- and c-Myc-dependent transactivation, consistent with gastrin- and PMA-induced activation of ERKs. Overexpression of wild type ERK-1 and ERK-2 or activation of endogenous ERKs using activated MEK-1 (mitogen-activated protein kinase kinase or ERK kinase) overexpression stimulated HDC promoter activity in a dose-dependent fashion. Interruption of the ERK-related pathway using expression vectors for kinase-deficient ERKs or an ERK-specific phosphatase (PAC-1) blocked gastrin- and PMA-stimulated HDC promoter activity. In contrast, inhibition of the Jun kinase pathway using an interfering dominant negative SEK-1 (stress-activated protein kinase/ERK-1) mutant did not inhibit HDC promoter activity. Furthermore, whereas gastrin stimulated phosphorylation of Shc proteins and association with Grb2, activation of the HDC promoter was not influenced by expression of dominant negative Ras (N15 or N17) proteins. However, gastrin stimulated Raf-1 kinase activity, and activation of the HDC promoter was blocked by coexpression of a dominant negative Raf-1 construct. Overall, these data demonstrate that gastrin regulates HDC transcription in a Rafdependent, Ras-independent fashion predominantly through activation of the ERK-related pathway.
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PMID:Gastrin and phorbol 12-myristate 13-acetate regulate the human histidine decarboxylase promoter through Raf-dependent activation of extracellular signal-regulated kinase-related signaling pathways in gastric cancer cells. 934 Nov 40

This report completes a preliminary analysis of the sequence of the 330,740-bp chlorella virus PBCV-1 genome, the largest virus genome to be sequenced to date. The PBCV-1 genome is 57% the size of the genome from the smallest self-replicating organism, Mycoplasma genitalium. Analysis of 74 kb of newly sequenced DNA, from the right terminus of the PBCV-1 genome, revealed 153 open reading frames (ORFs) of 65 codons or longer. Eighty-five of these ORFs, which are evenly distributed on both strands of the DNA, were considered major ORFs. Fifty-nine of the major ORFs were separated by less than 100 bp. The largest intergenic distance was 729 bp, which occurred between two ORFs located in the 2.2-kb inverted terminal repeat region of the PBCV-1 genome. Twenty-seven of the 85 major ORFs resemble proteins in databases, including the large subunit of ribonucleotide diphosphate reductase, ATP-dependent DNA ligase, type II DNA topoisomerase, a helicase, histidine decarboxylase, dCMP deaminase, dUTP pyrophosphatase, proliferating cell nuclear antigen, a transposase, fungal translation elongation factor 3 (EF-3), UDP glucose dehydrogenase, a protein kinase, and an adenine DNA methyltransferase and its corresponding DNA site-specific endonuclease. Seventeen of the 153 ORFs resembled other PBCV-1 ORFs, suggesting that they represent either gene duplications or gene families.
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PMID:Analysis of 74 kb of DNA located at the right end of the 330-kb chlorella virus PBCV-1 genome. 935 47

Helicobacter pylori infection of the gastric mucosa is accompanied by an activated histamine metabolism. Histamine plays a central role in the regulation of gastric acid secretion and is involved in the pathogenesis of gastroduodenal ulcerations. Histidine decarboxylase (HDC) is the rate-limiting enzyme for histamine production, and its activity is regulated through transcriptional mechanisms. The present study investigated the effect of H. pylori infection on the transcriptional activity of the human HDC (hHDC) promoter in a gastric epithelial cell line (AGS) and analyzed the underlying molecular mechanisms. Our studies demonstrate that H. pylori infection potently transactivated the hHDC promoter. The H. pylori-responsive element of the hHDC gene was mapped to the sequence +1 to +27 base pairs, which shows no homology to known cis-acting elements and also functions as a gastrin-responsive element. H. pylori regulates the activity of this element via a Raf-1/MEK/ERK pathway, which was activated in a Ras-independent manner. Furthermore, we found that H. pylori-induced transactivation of the hHDC promoter was independent of the cag pathogenicity island and the vacuolating cytotoxin A gene and therefore may be exerted through (a) new virulence factor(s). A better understanding of H. pylori-directed hHDC transcription can provide novel insights into the molecular mechanisms of H. pylori-dependent gene regulation in gastric epithelial cells and may lead to new therapeutic approaches.
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PMID:Helicobacter pylori activates the histidine decarboxylase promoter through a mitogen-activated protein kinase pathway independent of pathogenicity island-encoded virulence factors. 1065 59


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