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 secretagogue effect of prolactin (PRL) on casein release by epithelial mammary cells has been previously related to stimulation of the phospholipase A2-arachidonic acid cascade. In order to determine whether other intracellular pathways are implicated in this secretagogue effect, different agents acting on protein kinase C (PKC) and phospholipase C (PLC) activity have been assessed in vitro in lactating rabbit mammary gland fragments. Phorbol ester (20 nm TPA and 1-oleoyl-2-acetyl-sn-glycerol (10 microM (OAG) stimulated newly synthesized casein secretion and potentiated the PRL secretatogue effect. However, 100 microM quercetin, 100 microM H-7 and 5 and 20 nM staurosporine did not inhibit the latter effect. Exogenous PLC did not stimulate casein secretion. PRL did not affect production of inositol phosphates (IPs) during 10 or 60 min exposure. These results show that PKC activation may increase basal levels of casein secretion, and demonstrate that PRL does not act primarily via PKC activation or by PLC activation to stimulate casein secretion.
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PMID:The possible involvement of protein kinase C(s) and inositol phosphate metabolism in the basal but not in the prolactin stimulated casein release by the lactating rabbit mammary epithelial cell. 129 81

The normal mouse mammary epithelial cells, NOG-8, respond to the mitogenic signal of prolactin with a 2.5-fold increase in cell number within 3 days in vitro. When prolactin is added to subconfluent cells for 5-15 min, there is a 5-fold increase in protein kinase C activity. Upon longer exposure (24 h) to the hormone, the enzyme activity returns to that of control. The potent protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7), blocks both the prolactin-induced enzyme activity and subsequent increase in cell number. Prior to prolactin treatment, 90% of the protein kinase C activity resides in the cytosol with only 10% associated with the membranes. After only 5 min of prolactin treatment, 70% of the enzyme activity is now localized to the membranes. These data suggest that prolactin uses the protein kinase C pathway for signal transduction in NOG-8 cells thus leading to enhanced cell growth.
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PMID:Prolactin-induced protein kinase C activity in a mouse mammary cell line (NOG-8). 130 98

The effect of a number of steroids, growth factors, and peptides on aromatase activity in two estrogen receptor positive breast cancer cell lines (MCF7 and T47D) was investigated. The cells were incubated in Dulbecco's minimum essential medium containing phenol red and 10% fetal calf serum. Pronounced differences in basal aromatase activity and different responses to the addition of experimental agents were found in the two cell lines. Aromatase activity in MCF7 cells was significantly stimulated by phorbol 12,13-diacetate [PDA], dibutyryl cyclic AMP [(Bu)2cAMP], transforming growth factor alpha, and epidermal growth factor individually and PDA and (Bu)2cAMP in combination, while it was inhibited by dexamethasone and unaffected by transforming growth factor beta, fibroblast growth factor, platelet-derived growth factor, prolactin, and tamoxifen. Addition of cortisol to MCF7 cells had no effect on aromatase activity at 1 nM, caused suppression of activity at 10 nM and stimulated activity at 100 nM. Aromatase activity in T47D cells was stimulated by transforming growth factor alpha, epidermal growth factor, platelet-derived growth factor, prolactin, dexamethasone, and cortisol individually and PDA and (Bu)2cAMP in combination. It was unaffected by transforming growth factor beta, PDA, (Bu)2cAMP, and fibroblast growth factor. These findings suggest that aromatase activity is induced by agents which stimulate cyclic AMP-dependent protein kinases [e.g., (Bu)2cAMP] and that this effect is potentiated by factors which stimulate protein kinase C [e.g., PDA]. The effect on aromatase activity of growth factors, the actions of which are believed to be mediated by receptors linked to tyrosine kinase activity, is not as clearly defined, with a factor causing stimulation, inhibition, and no change in activity depending on the tissue concerned. Further insight into these differences will require resolution of the molecular mechanisms that mediate the actions of stimulatory and repressive growth factors on aromatase activity of oestrogen-producing cells.
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PMID:Steroid and growth factor modulation of aromatase activity in MCF7 and T47D breast carcinoma cell lines. 131 30

We have demonstrated that the novel hypothalamic peptide pituitary adenylate cyclase-activating polypeptide (PACAP-38; 0.1-100 nmol/l) caused an increase in the release of GH, ACTH, LH and alpha-subunit and accumulation of intracellular cyclic AMP from dispersed rat anterior pituitary cells in static culture for 24 h. There were no significant effects on TSH or prolactin release over the same time-period. PACAP-38 (10 nmol/l) increased the release of GH by 1.3-fold (P less than 0.05), ACTH by 1.9-fold (P less than 0.05), LH by 3.5-fold (P less than 0.001) and alpha-subunit by 2.0-fold (P less than 0.005) and the accumulation of intracellular cyclic AMP by greater than 2-fold (P less than 0.001) after 24 h. However, the time-course for the effect of PACAP-38 (1 mmol/l) on hormone release and intracellular cyclic AMP levels showed a temporal dissociation. The effect of PACAP-38 on GH and ACTH levels did not reach significance until 24 h whereas the effect of PACAP-38 on LH and alpha-subunit release reached significance after 4 h implying a different mechanism of action for their release. To investigate the PACAP-induced secretion of LH and alpha-subunit further, we examined the effects of PACAP after down-regulation of protein kinase C (PKC). PACAP-38 at a dose maximal for the stimulation of LH and alpha-subunit release (10 nmol/l) added together with the PKC activator, 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 0.1 mumol/l) had no greater effect on LH and alpha-subunit release than TPA alone over a 4 h incubation period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of a novel hypothalamic peptide, pituitary adenylate cyclase-activating polypeptide, on pituitary hormone release in rats. 138 57

Two protein kinase-inhibitors, 6-dimethyl amino purine and 2-amino purine inhibited induction of beta-casein synthesis by prolactin when added to the culture medium of rabbit mammary explant and cells. The accumulation of the mRNA for alpha s1- and beta-caseins and for whey acidic protein did not take place in the presence of the inhibitors whereas beta-actin mRNA concentration was not altered. In the same experimental conditions, H7, an inhibitor of protein kinase C and, to a lower extent, of protein kinase A did not prevent prolactin from acting. These data suggest for the first time that specific protein kinases are involved in the transduction of the prolactin signal to milk protein genes.
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PMID:6-Dimethyl amino purine and 2-amino purine inhibit the induction of expression of milk protein genes by prolactin. 139 84

Tail fin regression can be induced in anuran amphibians with L-thyroxine (T4). This regression can be antagonized with prolactin (PRL). Previous work had suggested that protein kinase C (PKC) was involved in PRL action. To address this issue further, the effect of a potent and selective inhibitor of protein kinase C on in vitro tail fin regression was investigated. T4-induced regression of tail fin pieces from Rana pipiens tadpoles could be antagonized by adding PRL or the PKC inhibitor H-7 to the medium. H-7 inhibited fin regression in a dose-dependent manner, with a half-maximal effective concentration of about 10(-5) M. The H-7 analogue, HA-1004 (which is not a selective inhibitor of PKC), was without effect. These results suggest a possible role for PKC in tail fin regression and may be useful in elucidating the antimetamorphic action of PRL.
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PMID:Inhibition of protein kinase C antagonizes in vitro tadpole tail fin regression induced by thyroxine. 139 14

In GH3 cells and other clonal rat pituitary tumor cells, TRH has been shown to mediate its effects on prolactin release via a rise of cytosolic Ca2+ and activation of protein kinase C. In this study, we examined the role of protein kinase C in TRH-stimulated prolactin release from female rat primary pituitary cell culture. Both TRH and PMA stimulated prolactin release in a dose-dependent manner. When present together at maximal concentrations, TRH and PMA produced an effect which was slightly less than additive. Pretreatment of rat pituitary cells with 10(-6) M PMA for 24 hrs completely down-regulated protein kinase C, since such PMA-pretreated cells did not release prolactin in response to a second dose of PMA. Interestingly, protein kinase C down-regulation had no effect on TRH-induced prolactin release from rat pituitary cells. In contrast, PMA-pretreated GH3 cells did not respond to a subsequent stimulation by either PMA or TRH. Pretreatment of rat pituitary cells with TRH (10(-7) M, 24 hrs) inhibited the subsequent response to TRH, but not PMA. Forskolin, an adenylate cyclase activator, stimulated prolactin release by itself and in a synergistic manner when incubated together with TRH or PMA. The synergistic effects of forskolin on prolactin release was greater in the presence of PMA than TRH. Down-regulation of protein kinase C by PMA pretreatment abolished the synergistic effect produced by PMA and forskolin but had no effect on those generated by TRH and forskolin. sn-1,2-Dioctanylglycerol (DOG) pretreatment attenuated the subsequent response to DOG and PMA but not TRH. The effect of TRH, but not PMA, on prolactin release required the presence of extracellular Ca2+. In conclusion, the mechanism by which TRH causes prolactin release from rat primary pituitary cells is different from that of GH3 cells; the former is a protein kinase C-independent process whereas the latter is at least partially dependent upon the activation of protein kinase C.
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PMID:PMA-sensitive protein kinase C is not necessary in TRH-stimulated prolactin release from female rat primary pituitary cells. 145 79

In GH4C1 rat pituitary cells, cell swelling stimulates prolactin (PRL) secretion by increasing Ca2+ influx through nifedipine-sensitive Ca2+ channels; however, the mechanism by which cell swelling opens Ca2+ channels is still unclear. To evaluate the role of protein kinase C (PKC) in this phenomenon, we studied the effect of down-regulating PKC by 12-h pretreatment with phorbol ester or by treatment with H-7, a protein kinase C inhibitor. Cell swelling induced by either 27% medium hyposmolarity or 80 mM isotonic urea caused a prompt rise in both [Ca2+]i and PRL secretion in otherwise untreated control GH4C1 cells. Removal of medium Ca2+ enhanced the osmotically induced cell swelling but prevented the increase in [Ca2+]i and PRL secretion. Both PKC down-regulation and H-7 suppressed the cell swelling-induced increases in [Ca2+]i concentration and PRL secretion, although they enhanced the induced cell volume expansion. Our data indicate that in GH4C1 cells PKC plays an important positive modulating role in the osmotic opening of plasmalemma Ca2+ channels, a critical component of the early transduction chain by which cell swelling causes PRL secretion in tumor-derived clonal pituitary cells.
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PMID:Protein kinase C modulates cell swelling-induced Ca2+ influx and prolactin secretion in GH4C1 cells. 151 83

A cultured myocardial cell model was used to examine the role of protein kinase C-dependent pathways in the transcriptional activation of two cardiac muscle genes [myosin light chain 2 (MLC-2) and atrial natriuretic factor (ANF)] during alpha-adrenergic receptor-mediated hypertrophy. Phorbol ester (phorbol 12-myristate 13-acetate) and the alpha-adrenergic agonist phenylephrine both activate protein kinase C (PKC) and induce 4- to 5-fold increases in the expression of MLC-2 and ANF promoter/luciferase reporter genes with little effect on Rous sarcoma virus/luciferase or minimal prolactin promoter/luciferase genes. To further assess the role of PKC in cardiac gene regulation, PKC expression vectors encoding constitutively activated PKC-alpha or PKC-beta, or a catalytically inactive PKC, were transiently cotransfected with the cardiac promoter/luciferase constructs. Cotransfection of either activated PKC-alpha or PKC-beta cDNA induces the expression of MLC-2 and ANF promoter/luciferase genes and of a reporter gene responsive to the transcription factor AP-1. The Rous sarcoma virus/luciferase and minimal prolactin promoter/luciferase genes are not concomitantly induced by cotransfectin with the PKC genes, indicating specificity of the transcriptional effect. The finding that activated PKC increases cardiac gene transcription suggests that activation of this enzyme may be a proximal signal for coregulation of two cardiac genes, MLC-2 and ANF, during the course of myocardial cell hypertrophy.
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PMID:Transcriptional activation of the cardiac myosin light chain 2 and atrial natriuretic factor genes by protein kinase C in neonatal rat ventricular myocytes. 153 37

The present study examines the effect of chronic dopamine treatment, known to inhibit prolactin release from anterior pituitary, on two Ca2+ and K+ currents in cultured rat lactotrophs. K+ and Ca2+ currents were recorded using the whole-cell mode of the patch-clamp technique. The two types of voltage-dependent Ca2+ currents are called SD and FD (slowly deactivating and fast deactivating current component, respectively) and the two types of voltage-dependent K+ currents, IA and IK. All current types were isolated by tail current analysis. The amplitude of both normalized calcium components depended on the length of the culture (n = 48) while normalized amplitudes of both potassium currents remained constant (n = 9). Incubation of cells during 72 h with 50 microM of Actinomycin D, an inhibitor of mRNA synthesis, suggested that this increase in Ca2+ currents involved the synthesis of proteins. Long-lasting D2 receptor stimulation (8 days; 10 nM RU 24213) prevented this selective effect through activation of a pertussis toxin-sensitive G protein. We also examined whether cyclic adenosine-3',5'-cyclic-monophosphate (cyclic AMP) or Ca2+/phospholipid-dependent protein kinase (protein kinase C) could affect this development of channel activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic stimulation of D2 dopamine receptors specifically inhibits calcium but not potassium currents in rat lactotrophs. 168 31


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