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:2.7.11.13 (protein kinase C)
49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied factors controlling message levels for the neuronal growth- and plasticity-associated protein, GAP-43. Following exposure of PC12 cells to various effectors, cytoplasmic RNA was isolated and analyzed by Northern transfer and autoradiography using a GAP-43 cDNA probe. Induction by NGF is apparent after 3 hr exposure and reaches maximal levels at 24 hr. Beyond 24 hr, levels remain constant in the continued presence of NGF. Induction is insensitive to variations in culture conditions, such as plating density or substrate, which influence NGF-induced neurite outgrowth. Other inducers, in order of decreasing efficacy, are FGF, dBcAMP, TPA, K+, and EGF. Insulin and retinoic acid are ineffective. Dexamethasone partially inhibited basal expression as well as induction by NGF, FGF, dBcAMP, and TPA. The methyltransferase inhibitor 5'-S-(2-methyl-propyl)adenosine completely inhibited induction by NGF, FGF, and dBcAMP. Inhibition of protein synthesis by cycloheximide partially decreased induction by NGF, FGF, and TPA but slightly enhanced dBcAMP induction. Complete down-regulation of protein kinase C by chronic TPA treatment completely eliminated the TPA response but slightly enhanced induction by NGF. These findings and the results of additivity experiments in which cells were stimulated with various combinations of NGF, dBcAMP and TPA suggest that NGF induction of GAP-43 RNA (1) does not involve activation of protein kinase C but (2) may be mediated partially via activation of protein kinase A.
...
PMID:Factors influencing GAP-43 gene expression in PC12 pheochromocytoma cells. 213 63

Resting human T lymphocytes do not express receptors for interleukin-2, but expression is rapidly induced by exposure to PHA. After maximal expression 2-3 days after stimulation, a progressive decline in receptor number is observed. Receptor expression can be augmented by reexposure to PHA. In this study we show that activators of protein kinase C including phorbol diester, phospholipase C, and the diacylglycerol congener diC8 also increase IL-2 receptor expression. Moreover, 5-azacytidine, which inhibits cytosine methyltransferase, and hydroxyurea, which inhibits ribonucleotide reductase, also increased receptor number. These studies demonstrate that IL-2 receptor expression can be altered in vitro, and that IL-2 receptor number, in combination with IL-2 secretion, may contribute to the regulation of IL-2-dependent immune responses.
...
PMID:Activators of protein kinase C and 5-azacytidine induce IL-2 receptor expression on human T lymphocytes. 258 Aug 52

Based on our recent finding that N,N-dimethyl-D-erythro-sphingenine strongly inhibits protein kinase C (PK-C) whereas D-erythro-sphingenine produces only weak inhibition, we have studied the presence of N-methyltransferase responsible for conversion of sphingosine to its N,N-dimethyl derivative. The enzyme activity was detected in crude mouse brain tissue homogenate but was hardly detectable in liver homogenate, in which N-methylation of phosphatidylethanolamine (PE) is predominant.
...
PMID:Enzymatic synthesis of N,N-dimethyl-sphingosine: demonstration of the sphingosine: N-methyltransferase in mouse brain. 268 39

When a partially purified rat liver phospholipid methyltransferase is incubated with [gamma-32P]ATP and rat brain protein kinase C, phospholipid methyltransferase (Mr 50,000, pI 4.75) becomes phosphorylated. Phosphorylation of the enzyme showed Ca2+/lipid-dependency. Protein kinase C-dependent phosphorylation of phospholipid methyltransferase was accompanied by an approx. 2-fold activation of the enzyme activity. Activity changes and enzyme phosphorylation showed the same time course. Activation of the enzyme also showed Ca2+/lipid-dependency. Protein kinase C mediates phosphorylation of predominantly serine residues of the methyltransferase. One major peak of phosphorylation was identified by analysis of tryptic phosphopeptides by isoelectrofocusing. This peak (pI 5.2) differs from that phosphorylated by the cyclic AMP-dependent protein kinase (pI 7.2), demonstrating the specificity of phosphorylation of protein kinase C. Tryptic-peptide mapping by h.p.l.c. of the methyltransferase phosphorylated by protein kinase C revealed one major peak of radioactivity, which could be resolved into two labelled phosphopeptides by t.l.c. The significance of protein kinase C-mediated phosphorylation of phospholipid methyltransferase is discussed.
...
PMID:Protein kinase C catalyses the phosphorylation and activation of rat liver phospholipid methyltransferase. 359 29

Localized juvenile periodontitis (ljp) is an early onset form of periodontal disease characterized by unique localization to first molars and incisors and a high prevalence of neutrophil abnormalities, particularly chemotaxis. The intracellular transduction mechanisms that follow receptor-ligand coupling on the neutrophil surface and lead to chemotaxis are not clearly established. Chemotaxis and phagocytosis are modulated by a variety of receptors and involve several activation pathways; the role of intracellular calcium as a presumptive second messenger and mediator of these events is well established. The putative effector mechanisms for the chemotactic receptor of neutrophils also include the possible activation of a phospholipase, protein kinase C, methyltransferase, or adenylate cyclase. In normal neutrophils, a phosphoinositide pathway initiated by phospholipase C, which results in the activation of protein kinase C via diacylglycerol and the generation of IP3, has been implicated. In order to better understand the stages of neutrophil transduction, fluorescent probes were used to monitor neutrophil calcium changes. Chlorotetracycline (CTC) was used as an indirect probe of intracellular membrane-bound pool of calcium stores, and Quin-2 was used to monitor cytosolic free calcium levels of FMLP stimulated normal and LJP neutrophils. The results indicate that the early phase of the calcium response affiliated with the release of intracellularly sequestered calcium appears intact in LJP neutrophils, as the CTC fluorescence changes were similar to control values. The second phase of the calcium response, associated with membrane channel activation and an influx of extracellular calcium, appeared compromised in the neutrophils of the LJP population.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Defective chemotaxis and calcium response in localized juvenile periodontitis neutrophils. 839 75

Prenylcysteine carboxymethyltransferase, an enzyme involved in the post-translational modification of many signalling proteins, was characterized in insulin-secreting INS-1 cells and normal rat pancreatic islets. The activity of this enzyme was monitored by the methylation of an artificial substrate (a prenylated cysteine analogue) with S-adenosy1[methyl-3H]methionine as methyl donor. More than 95% of the methyltransferase activity was associated with the membranes, and high-salt treatment only partially extracted the enzyme from the membranes. The highest specific activity was in the insulin-granule-enriched 25000 g pellet obtained by differential centrifugation. However, a highly purified insulin-enriched fraction obtained by density centrifugation in Percoll did not exhibit methyltransferase activity. The analyses of marker enzymes for cellular organelles revealed that the methyltransferase was co-localized, with the plasma membrane and probably the endoplasmic reticulum, but not with the mitochondria or lysosomes. Guanosine 5'-[gamma-thio]-triphosphate failed to increase methyltransferase activity directly, although it promotes the methylation of GTP-binding proteins. Mastoparan, Ca2+, cAMP and the protein kinase C activator phorbol 12-myristate 13-acetate did not alter enzyme activity. In addition, methyltransferase activity was not stably modified by stimulation of intact cells using glucose or other agents. However, the carboxymethylation of certain low-molecular-mass G-proteins is increased by glucose stimulation; conversely, treatment of cells with N-acetyl-S-trans,trans-farnesyl-L-cysteine inhibited glucose- and forskolin-induced insulin secretion. These results suggest that the membrane-associated prenylcysteine carboxymethyltransferase may be constitutively active and that the methylation of target proteins in vivo is regulated by the access of these proteins to the methyltransferase, as well as by their active (GTP-liganded) configuration.
...
PMID:Characterization of prenylcysteine methyltransferase in insulin-secreting cells. 864 28

Parathyroid hormone (PTH)-mediated gene activation was assessed in the osteoblast-like rat cell line ROS17/2.8 with two PTH fragments harboring distinct activating domains: PTH-(1-34) and PTH-(28-48). The PTH response of genes expressed immediate early in the cell cycle or in the osteoblast developmental sequence was investigated. In addition, subtractive cloning was used to identify genes in ROS17/2.8 cells that are activated by the two PTH domains. PTH-(1-34) immediately increased the transcript levels of c-fos and c-jun at a considerably higher rate than PTH-(28-48). A significant immediate PTH effect on osteoblastic marker genes could not be detected, with the exception of elevated ornithine decarboxylase transcript levels. However, continuous application of PTH-(1-34) increased transcript levels of the osteoblast-specific osteocalcin gene and reduced those of other osteoblastic marker genes including alkaline phosphatase and the PTH/PTH-related peptide receptor. By subtractive cloning, nine cDNAs were isolated corresponding to mRNAs directly up-regulated by PTH-(1-34) or PTH-(28-48). Among these were a cyclic phosphodiesterase, a (cytosine 5)-methyltransferase, an 80-kDa protein kinase C substrate, junB, and a novel GC-binding protein. Three cDNAs are unknown at present. Interestingly, in all cases, the efficiency of gene activation by PTH-(28-48) was substantially lower in comparison with PTH-(1-34). PTH-mediated protein kinase C signaling in ROS17/2.8 cells may therefore constitute a minor pathway in comparison with the dominant cAMP/protein kinase A cascade.
...
PMID:Domain-specific gene activation by parathyroid hormone in osteoblastic ROS17/2.8 cells. 870 88

Prenylated protein methyltransferase, an enzyme involved in the post-translational modification of many signalling proteins, has been characterized in a parasitic flagellated protozoan, Leishmania donovani. The activity of this enzyme was monitored by the methylation of an artificial substrate, an S-prenylated cysteine analogue, with S-adenosyl-l-[methyl-(3)H]methionine as methyl donor. More than 85% of the methyltransferase activity was associated with membranes. The enzyme methylates N-acetyl-S-trans, trans-farnesyl-l-cysteine and N-acetyl-S-all-trans-geranylgeranyl-l-cysteine, but N-acetyl-S-trans, trans-geranyl-l-cysteine only very weakly. In contrast with the enzyme from mammals, the leishmanial enzyme had a greater affinity for the farnesylated substrate than for the geranylgeranylated one. Activity in vitro was not modulated by cAMP, protein kinase C activator or guanosine 5'-[gamma-thio]triphosphate. An analysis of the endogenous substrates showed that the carboxymethylated proteins were also isoprenylated. The main carboxymethylated proteins have molecular masses of 95, 68, 55, 46, 34-23, 18 and less than 14 kDa. Treatment of cells with N-acetyl-S-trans,trans-farnesyl-l-cysteine decreased the carboxymethylation level, whereas treatment with guanosine 5'-[gamma-thio]triphosphate increased the carboxymethylation of various proteins, particularly those of molecular masses 30-20 kDa.
...
PMID:Characterization of prenylated protein methyltransferase in Leishmania. 1047 61

Chronic lymphocytic leukemia therapy has changed dramatically over the past decade, with recent studies supporting the use of fludarabine as the initial therapy for symptomatic disease. New findings relative to the use of fludarabine and complications arising from this therapy are reviewed. Exciting combination approaches using monoclonal antibodies such as rituximab or Campath-1H in combination with fludarabine offer the opportunity to improve the complete response rate further in chronic lymphocytic leukemia. Furthermore, the field of experimental therapeutics for chronic lymphocytic leukemia was advanced by the description of a new mouse model of human chronic lymphocytic leukemia and identification of several disrupted signal transduction pathways in this disease. The description of therapies that target AKT, protein kinase C, phosphodiesterase 4, mammalian target of rapamycin, histone deacetylase, and methyltransferase offer the opportunity to utilize molecularly targeted therapy for this disease. Such targeted approaches offer hope that we might be on the threshold to changing the natural history of chronic lymphocytic leukemia.
...
PMID:Advances in the therapy of chronic lymphocytic leukemia. 1279 36

The bryostatins are protein kinase C modulators with unique structural features and potential anticancer and neurological activities. These complex polyketides were isolated from the marine bryozoan Bugula neritina, but recent studies indicate that they are produced by the uncultured symbiotic bacterium "Candidatus Endobugula sertula" ("E. sertula"). Here we present the putative biosynthetic genes: five modular polyketide synthase (PKS) genes, a discrete acyltransferase, a beta-ketosynthase, a hydroxy-methyl-glutaryl CoA synthase (HMG-CS), and a methyltransferase. The cluster was sequenced in two closely related "E. sertula" strains from different host species. In one strain the gene cluster is contiguous, while in the other strain it is split into two loci, with one locus containing the PKS genes and the other containing the accessory genes. Here, we propose a hypothesis for the biosynthesis of the bryostatins. Thirteen PKS modules form the core macrolactone ring, and the pendent methyl ester groups are added by the HMG-CS gene cassette. The resulting hypothetical compound bryostatin 0 is the common basis for the 20 known bryostatins. As "E. sertula" is to date uncultured, heterologous expression of this biosynthetic gene cluster has the potential of producing the bioactive bryostatins in large enough quantities for development into a pharmaceutical.
...
PMID:Identification of the putative bryostatin polyketide synthase gene cluster from "Candidatus Endobugula sertula", the uncultivated microbial symbiont of the marine bryozoan Bugula neritina. 1725 52


1 2 3 Next >>

---