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)

The presence of protein kinase C (PKC), a key enzyme in signal transduction, has not been investigated in fungal cells. The phorbol ester TPA, an activator of PKC, may be used as an indicator of the presence and role of PKC in Phycomyces blakesleeanus spores. Activation of spore germination by acetate was prevented by 6 nM TPA. The TPA analog 4 alpha PDD, an ineffective activator of PKC, did not affect spore germination. 3 mM dbcAMP, on the other hand, reversed the inhibition of germination caused by TPA. TPA-stimulated protein kinase activity was detected in spores. The possible relationship between PKC and the increased levels of cAMP that accompany the induction of spore germination is discussed.
 ...
PMID:12-O-tetradecanoyl phorbol-13-acetate interferes with germination of Phycomyces blakesleeanus sporangiospores. 284 10

The effects of the active phorbol ester 12-myristate, 13-acetate (PMA), the inactive ester 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), and the synthetic diacylglycerol 1-oleoyl-2-acetyl-glycerol (OAG) on cyclic AMP production were examined in rat cerebral cortical and diencephalic cells. With the aid of a prelabeling technique for measuring cyclic AMP accumulation in the cells, it was found that neither PMA nor OAG significantly increased cyclic AMP formation in either type of cell. In contrast, PMA enhanced the cyclic AMP response to vasoactive intestinal peptide (VIP) and forskolin in cerebral cortical and diencephalic cells, whereas 4 alpha-PDD was inactive. A 15-min preincubation was used to obtain maximal enhancement. The concentration dependence of PMA on VIP-stimulated cyclic AMP accumulation was determined in cortical cells (EC50 = 6.2 x 10(-8) M). OAG was also able to potentiate VIP-induced cyclic AMP formation in cortical and diencephalic cells. However, its potentiating effect was weaker than that observed with PMA treatment. The data show, at an early stage of development (primary cultures, 8-10 days), a modulation of VIP- or forskolin-cyclic AMP response by the activators of protein kinase C, i.e., PMA and OAG, in two different structures of the central nervous system: the cerebral cortex and the diencephalon. To our knowledge, this is the first demonstration of such a potentiation within the diencephalon.
 ...
PMID:Activators of protein kinase C enhance cyclic AMP accumulation in cerebral cortical and diencephalic neurons in primary culture. 284 13

To clarify the possible role of protein kinase C in the control of parathyroid hormone (PTH)-degrading activity (PTHDA) in a PTH-responsive opossum kidney (OK) cell line, we investigated the effects of protein kinase C activators, 12-O-tetradecanoyl phorbol 13-acetate (TPA), 1-oleoyl-2-acetyl-glycerol (OAG), and 4 beta-phorbol 12, 13-didecanoate (4 beta-PDD). TPA, OAG, and 4 beta-PDD enhanced PTHDA in a dose-dependent fashion (10-50 ng/ml, 10-100 microgram/ml, and 10-50 nM, respectively), whereas 4 alpha-PDD, a non-activator of protein kinase C, did not affect it. HPLC analysis of TPA-treated samples revealed increase of all immunoreactive PTH fragments produced by OK cells. These findings suggested that activation of protein kinase C in OK cells would augment PTHDA in the cells.
 ...
PMID:Control of parathyroid hormone-degrading activity in the opossum kidney cell: possible involvement of protein kinase C. 284 46

The hypothesis that protein kinase C may be an important regulator of ovarian theca-interstitial cell steroidogenesis was tested by using phorbol-12-myristate-13-acetate (PMA) and phorbol-12, 13-dibutyrate (PDB) to directly stimulate protein kinase C activity. Collagenase-dispersed cells (4 x 10(5) viable cells/dish) form ovaries of hypophysectomized immature rats were cultured in serum-free medium in the presence and absence of 0-100 ng/ml of luteinizing hormone (LH), PMA (0-100 nM), and/or PDB (0-100 nM). Treatment with 100 ng/ml LH stimulated androsterone production 100-fold at Day 4 of culture. The presence of 100 nM PMA or PDB had no effect on basal androsterone production; however, treatment with increasing concentrations of PMA or PDB (0-100 nM) caused a dose-related inhibition (maximum 70%) of LH-stimulated androsterone synthesis (ID50 = 1.8 nM and 2.4 nM, respectively). PMA and PDB did not significantly alter DNA, protein, or cell viability, indicating that their inhibitory effects were not due to changes in cell number or viability. Cells treated with LH and 100 nM 4 alpha-phorbol didecanoate (4 alpha-PDD; a phorbol ester that does not activate protein kinase C) failed to show significant decreases in androsterone production. Time-course studies revealed that when PMA treatment was delayed until Day 2 or 4 of culture, dramatic inhibitory effects on LH-stimulated androsterone production were still observed. These results suggest that the biological activity of protein kinase C is retained after the cells have expressed their differentiated state.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Evidence for protein kinase C regulation of ovarian theca-interstitial cell androgen biosynthesis. 285 24

Exposure of polymorphonuclear neutrophils (PMNs) to phorbol 12-myristate 13-acetate (PMA) resulted in a concentration-dependent (1-10 ng/ml) inhibition of granule exocytosis induced with the receptor-specific ligands, N-formyl-methionyl-leucyl-phenylalanine (FMLP), pepstatin A, 5(S),12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid (LTB4), and acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC). PMA exerted a marginal inhibitory effect on calcium ionophore A23187-induced PMN degranulation, and the PMA analog, 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), was inactive. However, PMA potentiated AGEPC, pepstatin A, FMLP, LTB4, and A23187-stimulated superoxide anion (O2-) production. The mobilization of intracellular sequestered calcium (Ca2+) by the receptor-specific ligands, as reflected by a rise in the cytosolic-free Ca2+ concentration ([Ca2+]i) in PMNs loaded with the Ca2+-sensitive dye, Fura-2, was suppressed by PMA. A protein kinase C (PKC) inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) reversed the PMA-mediated inhibition of PMN degranulation and intracellular CA2+ mobilization. However, another, but less potent PKC inhibitor, N-(2-guanidino-ethyl)-5-isoquinolinesulfonamide (HA1004), had no effect on the inhibition of PMN activation by PMA.
 ...
PMID:Function and stimulus-specific effects of phorbol 12-myristate 13-acetate on human polymorphonuclear neutrophils: autoregulatory role for protein kinase C in signal transduction. 285 53

The phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) was used to examine the hypothesis that phosphoinositide turnover is involved in the regulation of myocardial contractility mediated by stimulation of alpha-adrenoceptors in the mammalian cardiac muscle. Exposure of the isolated rabbit papillary muscle electrically driven at a rate of 1 Hz at a temperature of 37 degrees C to TPA in concentrations of 10-1000 nmol/l for 30 min did not affect the basal force of contraction. The concentration-response curve for the positive inotropic effect of (-)-phenylephrine mediated by stimulation of alpha-adrenoceptors in the presence of (+/-)-bupranolol (100 nmol/l) was shifted to the right and downward by TPA in concentrations of 30-1000 nmol/l, while the effect of (-)-phenylephrine mediated by stimulation of beta-adrenoceptors in the presence of prazosin (100 nmol/l) was not decreased, but slightly enhanced by exposure of the muscle to relatively low concentrations of TPA (10-100 nmol/l). Incubation of the membrane fraction isolated from the rabbit ventricular muscle with TPA in vitro under the same condition as employed in the physiological experiments decreased the specific binding of [3H]prazosin but not that of [3H]CGP-12177, while the non-tumor promoting phorbol ester, alpha PDD, was ineffective. These results indicate that activation of protein kinase C by TPA does not mimic the positive inotropic effect of catecholamines mediated by activation of myocardial alpha-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Phorbol ester does not mimic, but antagonizes the alpha-adrenoceptor-mediated positive inotropic effect in the rabbit papillary muscle. 289 86

Functional gastrin-containing tumor cells (GT cells) have been maintained in short-term culture on microporous membranes, and their response to selected agents has been determined. After dispersion of gastrinoma by collagenase-DNAase digestion coupled with mechanical disruption, dispersed cells were depleted in stromal material by selective attachment to a plastic substrate, then cultured for 72 hours on porous cellulose membranes. Cultures contained 68 +/- 5% GT cells with a viability of 92 +/- 2%. Secretin stimulated the rate of gastrin release from cultured GT cells in both a time- and a dose-dependent fashion. To examine the possible involvement of adenylate cyclase- and protein kinase C-mediated mechanisms in regulating gastrin release from the neoplastic GT cells, we evaluated the effects of 8-bromoadenosine 3':5'-cyclic monophosphate (8-BrcAMP; 10(-4) - 10(-2) mol/L), the diterpene forskolin (10(-5) mol/L), 12-0-tetradencanoylphorobol 13-acetate (TPA; 10(-8) - 10(-6) mol/L), and 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD; 10(-8) - 10(-6) mol/L) on gastrin release. Among all compounds tested, 8-BrcAMP (10(-2) mol/L) was the most potent, stimulating the rate of gastrin release 263% above basal. Both 8-BrcAMP and TPA stimulated gastrin release in a dose-dependent fashion. The biologically inactive phorbol ester, 4 alpha PDD, was without effect at all concentrations. Somatostatin (10(-8) - 10(-6) mol/L) inhibited 8-BrcAMP-stimulated gastrin release in a dose-dependent fashion to a maximum of 75%.
 ...
PMID:Control of gastrin release in cultured gastrinoma-derived G cells. 289 16

The phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) enhances the effects of TRH on phase II of prolactin secretion as well as on hormone synthesis at both low and high TPA receptor occupancy. Furthermore TPA, but not the biologically inactive substance 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), stimulates the particulate bound adenylate cyclase with a time course paralleling that of TRH activation. However, the combined additions of TRH and TPA activate this cyclase in an additive manner while the Gpp(NH)p- and the forskolin-sensitive enzyme are unaffected by TPA addition. Polymyxin B, which inhibits protein kinase C, abolishes activation of adenylate cyclase by TPA without interfering with the stimulatory action of TRH. Also, when phosphatase activity is preferentially inhibited by pretreatment of the cells with sodium vanadate, the TRH-sensitive cyclase is unaltered, while TPA activation is obliterated. Maximal stimulation of adenylate cyclase by cholera toxin pretreatment, obliterated the actions of TRH and TPA. Cells pretreated with pertussis toxin retained their TRH-sensitive cyclase, however, TPA-responsiveness was lost. We therefore suggest that the action of TPA as it relates to activation of adenylate cyclase, is probably mediated via the Gi component of the adenylate cyclase complex, while TRH stimulates the enzyme via the classical pathway involving the stimulatory GTP binding protein (Gs).
 ...
PMID:Phorbol esters and thyroliberin have distinct actions regarding stimulation of prolactin secretion and activation of adenylate cyclase in rat pituitary tumour cells (GH4C1 cells). 290 8

In this work we found that the induction of tyrosine aminotransferase by glucocorticoid in rat hepatocytes was suppressed concentration-dependently by TGF-beta and H-7, an inhibitor of protein kinase C, but not by other polypeptide growth factors tested or by H-8, an inhibitor of cyclic nucleotide dependent protein kinases. EGF, on the contrary, amplified the induction in the same way as activators of protein kinase C, such as 12-o-tetradecanoyl-phorbol 13-acetate (2,3) and 1,2-racemic dioctanoyl glycerol (1,3). These findings indicate that TGF-beta and H-7 act in the suppressive direction and EGF acts in the enhance direction on the action of glucocorticoid. H-7 inhibited the accumulation of glucocorticoid-receptor complexes in the nuclear fraction with associated accumulation of these complexes in the cytoplasmic fraction, but did not affect incorporation of glucocorticoid into hepatocytes. These results suggest that protein kinase C is essential in translocation of glucocorticoid-receptor complexes to the nuclei and that its inhibitors suppress glucocorticoid actions.
 ...
PMID:Studies on biomodulators of glucocorticoid action: amplifiers and suppressors of glucocorticoid action. 290 66

The active tumor promoters, 12-O-tetradecanoyl phorbol 13-acetate (TPA) and phorbol 12, 13-dibutyrate (PDBu), which activate protein kinase C (PKC), were found to stimulate bovine brain cortex capillary endothelial cell (CEC) proliferation in a dose-dependent manner. 4 alpha-phorbol-12, 13-didecanoate (4 alpha-PDD), known to be inactive for PKC, was without effect in stimulating CEC proliferation. Furthermore, prolonged incubation with TPA led to a decrease in the number of [3H]-PDBu binding sites with a parallel loss of responses of the cells to TPA. Finally, staurosporine, a potent PKC inhibitor, showed a strong antiproliferative effect on CEC (IC50 = 1.3 nM). Therefore, this work suggests that PKC plays a fundamental role in CEC growth.
 ...
PMID:Tumor-promoting phorbol esters stimulate bovine cerebral cortex capillary endothelial cell growth in vitro. 291 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>