Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The human endothelin-1 (ET-1) gene, which is located on chromosome 6, contains cis-regulatory elements in the 5'-flanking region including the TPA-responsive element, nuclear factor 1 binding element and GATA motif. 2. The expression of preproendothelin-1 (PPET-1) mRNA is regulated by a mechanism involving receptor mediated mobilization of intracellular Ca2+ and activation of protein kinase C in endothelial cells. 3. Activation of protein kinase C results in the synthesis of c-Jun protein and the rapid dephosphorylation of c-Jun protein. Consequently, the binding activity of c-Jun protein to the TPA-responsive element increases, and this causes the induction of PPET-1 mRNA. 4. The microtubular system seems to play some important roles in ET-1 secretion, especially in the process of transferring the synthesized ET-1 to the cell surface of the endothelial cells. 5. The secretion of ET-1 from endothelial cells is also regulated by intracellular Ca2+ released from the Ca2+ store and by Ca2+-calmodulin complex. The phosphorylation of the myosin light chain, elicited by myosin light chain kinase and activated by Ca2+-calmodulin complex, facilitates the formation of filamentous myosin and actin which probably participate in ET-1 secretion especially in transporting the ET-1-containing vesicles towards the cell membrane in the stimulated endothelial cells. 6. Many cultured cells, other than endothelial cells, also secret ET-1 into the culture medium and this secretion can be stimulated by a variety of agents.
Gen Pharmacol 1994 Oct
PMID:The control of endothelin-1 secretion. 787 27

1. The saponin-permeabilized platelet was used to examine the effect of mezerein, a moderate activator of protein kinase C (C-kinase), on the sequestration of Ca2+ to its intracellular storage sites. 2. We found that the activation of C-kinase by mezerein causes the potentiation of the Ca2+ sequestration. 3. It was suggested that C-kinase in platelets might function as a negative feedback regulator for the agonist-induced Ca2+ mobilization and might be involved in its oscillation.
Gen Pharmacol 1994 May
PMID:Stimulation of calcium sequestration by mezerein, a protein kinase C activator, in saponized rabbit platelets. 792 83

1. This study examined the ability of various nitro-vasodilators, 8-bromo cyclic guanosine 3':5' monophosphate (8-BrcGMP) and forskolin to relax rings of rat thoracic aorta pre-contracted with either noradrenaline (0.1 microM) or the protein kinase C activators, phorbol 12,13-dibutyrate (PDB, 0.1 microM) or phorbol 12-myristate 13-acetate (PMA, 0.5 microM). 2. In noradrenaline pre-contracted rings, acetylcholine (10 nM-10 microM), sodium nitroprusside (1 nM-0.5 microM), the calcium ionophore A23187 (10 nM-10 microM) and 8-BrcGMP (10 mM) totally reversed the smooth muscle contraction. In PDB-contracted aortic rings acetylcholine, sodium nitroprusside and 8-BrcGMP-induced relaxation was reduced compared to that in noradrenaline-contracted aortic rings, but A23187 and forskolin-induced relaxations were unaffected. Both acetylcholine and A23187-induced relaxations in PDB-contracted rings were abolished in the presence of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine (NOLA, 100 microM). 3. Acetylcholine and sodium nitroprusside were even less potent in their ability to relax PMA-contracted aortic rings compared with noradrenaline and PDB-contracted rings. A23187-induced relaxation was also inhibited in PMA-contracted rings. 4. These results show that protein kinase C activation reduces the ability of agents which liberate nitric oxide to induce smooth muscle relaxation, and also inhibits the biochemical pathways which are subsequently activated by nitric oxide and lead to vascular smooth muscle relaxation.
Gen Pharmacol 1994 May
PMID:Phorbol esters impair endothelium-dependent and independent relaxation in rat aortic rings. 792 9

1. Effects of phorbol esters (stimulators of protein kinase C, PK-C) on the L-type Ca2+ current (ICa) and the intracellular Ca2+ level ([Ca]i) were investigated using single rabbit sino-atrial (SA) node cells. 2. In whole-cell patch-clamp experiments, both phorbol esters (1 microM). 4-beta-phorbol-12,13-dibutyrate (PDB) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA), inhibited the ICa. Phorbol esters did not affect the voltages of half-maximum activation and inactivation for ICa. 3. The time-course of inactivation phase for ICa was two exponentials. The fast component was decreased, whereas the slow component was increased by phorbol esters. 4. Addition of H-7 (10 microM), an inhibitor of PK-C, did not antagonize, but rather increased both components. In contrast, 4-alpha-phorbol-12,13-didecanoate (PDD), an inactive analog, did not affect the ICa amplitude and the inactivation process. 5. The phorbol esters elicited a transient inward current by repetitive clamp pulses. 6. In SA node cells loaded with fura-2 (a Ca(2+)-sensitive fluorescent dye), both TPA and PDB at 0.3 microM in the presence of isoproterenol (ISP, 0.2 microM) elevated the [Ca]i. PDD did not affect [Ca]i. 7. These results indicate that PK-C stimulation by phorbol esters elevates [Ca]i (which is potentiated by ISP), possibly resulting in cellular calcium overload.
Gen Pharmacol 1994 Mar
PMID:Elevation of intracellular Ca2+ concentration by protein kinase C stimulation in isolated single rabbit sino-atrial node cells. 802 32

Effects of neurotransmitters on cAMP-mediated signal transduction in frog olfactory receptor cells (ORCs) were studied using in situ spike recordings and radioimmunoassays. Carbachol, applied to the mucosal side of olfactory epithelium, amplified the electrical response of ORCs to cAMP-generating odorants, but did not affect unstimulated cells. A similar augmentation of odorant response was observed in the presence of phorbol dibutyrate (PDBu), an activator of protein kinase C (PKC). The electrical response to forskolin, an activator of adenylate cyclase (AC), was also enhanced by PDBu, and it was attenuated by the PKC inhibitor Goe 6983. Forskolin-induced accumulation of cAMP in olfactory tissue was potentiated by carbachol, serotonin, and PDBu to a similar extent. Potentiation was completely suppressed by the PKC inhibitors Goe 6983, staurosporine, and polymyxin B, suggesting that the sensitivity of olfactory AC to stimulation by odorants and forskolin was increased by PKC. Experiments with deciliated olfactory tissue indicated that sensitization of AC was restricted to sensory cilia of ORCs. To study the effects of cell Ca2+ on these mechanisms, the intracellular Ca2+ concentration of olfactory tissue was either increased by ionomycin or decreased by BAPTA/AM. Increasing cell Ca2+ had two effects on cAMP production: (a) the basal cAMP production was enhanced by a mechanism sensitive to inhibitors of calmodulin; and (b) similar to phorbol ester, cell Ca2+ caused sensitization of AC to stimulation by forskolin, an effect sensitive to Goe 6983. Decreasing cell Ca2+ below basal levels rendered AC unresponsive to stimulation by forskolin. These data suggest that a crosstalk mechanism is functional in frog ORCs, linking the sensitivity of AC to the activity of PKC. At increased activity of PKC, olfactory AC becomes more responsive to stimulation by odorants, forskolin, and cell Ca2+. Neurotransmitters appear to use this crosstalk mechanism to regulate olfactory sensitivity.
J Gen Physiol 1993 Feb
PMID:Protein kinase C sensitizes olfactory adenylate cyclase. 809 69

1. Accumulation of [3H]-inositol phosphates (IPs) was slightly enhanced by PAF in a concentration-dependent manner, but the accumulation was very small as compared with that induced by carbachol. 2. The levels of [32P]-phosphatidic acid which is transformed from diacylglycerol (DAG) were increased by treatment with PAF or with carbachol. 3. PAF-induced contraction was significantly reduced by treatment with phorbol 12-myristate 13-acetate (PMA). 4. These results suggest that while PAF slightly stimulates the turnover of phosphatidylinositol (PI) in the rat stomach fundus, this response may not be responsible for the PAF-induced contractile response, and that the desensitization induced by repeated application of PAF may be due to the activation of protein kinase C.
Gen Pharmacol 1993 Nov
PMID:Mechanism of the contractile response to platelet-activating factor (PAF) of the rat stomach fundus. II. PAF-induced phosphatidylinositol turnover and desensitization. 811 4

The aim of this work was to study the relationships among protein kinase C (PKC), calcium, prostaglandins (PGs), and sex steroids in follicles of Rana esculenta and Triturus carnifex. Follicles, oocytes, and wall cells of follicle (theca and granulosa cells) were incubated in vitro with an activator of PKC, phorbol-12-myristate-13-acetate (PMA), a calcium ionophore (A23187), an antagonist of calcium channel, verapamil, PMA + A23187, prostaglandin F2 alpha (PGF2 alpha), and prostaglandin E2 (PGE2). Progesterone, androgens, and 17 beta-estradiol were assessed in incubation media of follicles and wall cells and PGs in incubation media of follicles, oocytes, and wall cells. In both species, PMA increased progesterone; A23187 increased progesterone, 17 beta-estradiol, and PGs; verapamil decreased progesterone and PGs; PMA + A23187 increased progesterone, 17 beta-estradiol, and PGs; PGF2 alpha increased 17 beta-estradiol; PGE2 increased progesterone. These data suggest that PKC and calcium intervene in the regulation of steroidogenesis and PG synthesis by follicles of both R. esculenta and T. carnifex; in particular, calcium seems to regulate PGs synthesis, activating an enzymatic pathway which does not include PKC.
Gen Comp Endocrinol 1994 Jan
PMID:A phorbol ester and calcium ionophore regulate sex steroid and prostaglandin release by follicles of the anuran Rana esculenta and the urodele Triturus carnifex. 813 11

To investigate the effect of persistent measles virus infection on signal transduction in cells of neuronal origin, the mouse neuroblastoma cell line NS20Y/MS, which is persistently infected with measles virus, was used. The results demonstrate an approximate 50% increase in total phosphorylation and a similar increase in protein kinase C (PKC) activity. Western blot analysis with anti-total PKC or anti-PKC-alpha antibodies revealed a significant increase in the level of an 80K immunoreactive PKC in NS20Y/MS cells. Following incubation of NS20Y/MS cells with polyclonal anti-measles virus antibodies, which down-regulate the level of measles virus proteins, total and PKC-mediated phosphorylation returned to the basal level of uninfected cells. This effect was reversible and removal of the antibodies resulted in restoration of the high level of total and PKC-mediated phosphorylation. The release of infectious measles virus was strongly inhibited by incubation of NS20Y/MS cells with the PKC inhibitor, 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H-7). These results demonstrate that measles virus induces elevation in cellular phosphorylation which is essential for measles virus production.
J Gen Virol 1994 Apr
PMID:Reversal of the measles virus-mediated increase of phosphorylating activity in persistently infected mouse neuroblastoma cells by anti-measles virus antibodies. 815 Dec 98

Loss of yeast protein kinase C function results in three distinct phenotypes: staurosporine sensitivity, cell lysis and blockage of cell cycle progression at the G2/M boundary. Genetic analysis of the PKC1/STT1 protein kinase C gene and its interactions with STT4, encoding an upstream phosphatidylinositol 4-kinase, and BCK1, encoding a downstream protein kinase, reveal that they form part of a single pathway. However, the BCK1-20 mutation (a gain-of-function mutation of BCK1) or overexpression of PKC1 cannot suppress all of the phenotypes caused by the loss of STT4 function, strongly suggesting the existence of a branch point between STT4 and PKC1. We also describe the MSS4 gene, a multicopy suppressor of the temperature-sensitive stt4-1 mutation. MSS4 is predicted to encode a hydrophilic protein of 779 amino acid residues and is essential for cell growth. Based on genetic and biochemical data, we suggest that MSS4 acts downstream of STT4, but in a pathway that does not involve PKC1.
Mol Gen Genet 1994 Mar
PMID:Genetic interactions among genes involved in the STT4-PKC1 pathway of Saccharomyces cerevisiae. 815 13

To obtain more information about the cell wall organization of Saccharomyces cerevisiae, we have developed a novel screening system to obtain cell wall-defective mutants, using a density gradient centrifugation method. Nine hypo-osmolarity-sensitive mutants were classified into two complementation groups, hpo1 and hpo2. Phase contrast microscopic observation showed that mutant cells bearing lesions at either locus became abnormally large. A gene that complemented the mutant phenotype of hpo2 was cloned and sequenced. This gene turned out to be identical to PKC1, which encodes the yeast homologue of mammalian protein kinase C. Complementation tests with pkc1 delta showed that hpo2 is allelic to pkc1. To study the reason for the fragility of hpo2 cells, cell wall was isolated and the glucan was analyzed. The amount of alkali, acid-insoluble glucan, which is responsible for the rigidity of the cell wall, was reduced to about 30% that of the wild-type cell and this may be the major cause of the fragility of the hpo2 mutant cell. Analysis of total wall proteins in hpo2 mutant cells on SDS-polyacrylamide gels revealed that a 33 kDa protein was overproduced two- to threefold relative to the wild-type level. This 33 kDa protein was identified as a beta-glucanase, encoded by BGL2. Disruption of BGL2 in the hpo2 mutant partially rescued the growth rate defect. This suggests that the PKC1 kinase cascade regulates BGL2 expression negatively and overproduction of the beta-glucanase is partially responsible for the growth defect.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Gen Genet 1994 Mar
PMID:The hypo-osmolarity-sensitive phenotype of the Saccharomyces cerevisiae hpo2 mutant is due to a mutation in PKC1, which regulates expression of beta-glucanase. 815 14


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