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 Y1 receptor for neuropeptide Y (NPY-Y1) is constitutively expressed in PC12 cells. In this study, we examined the role of nerve growth factor (NGF), pituitary adenylyl cyclase activating polypeptide (PACAP) and dexamethasone on the expression of the gene encoding the rat NPY-Y1 receptor in PC12 cells. A fusion gene (pY1-Luc) was constructed where the reporter enzyme firefly luciferase was placed under the control of 700 bp of the promoter region of the rat NPY-Y1 receptor gene. This promoter region contains recognition consensus sequences for various transcription factors, including one activation protein-1 (AP-1) site, two cyclic AMP responsive element sites, one estrogen receptor element site and four glucocorticoid receptor element sites. NGF increased luciferase activity in a concentration dependent manner. This increase was inhibited by K-252a, a trk A receptor inhibitor, and calphostin C, a PKC inhibitor. PACAP-38 increased luciferase activity in a concentration dependent manner. This activation was inhibited by H-89. Dexamethasone increased transcription of NPY-Y1 gene in PC12 cells. These results indicate that differentiation of PC12 cells into endocrine-like phenotype by dexamethasone and into a neuronal-like phenotype by either NGF or PACAP-38 increases the transcriptional activity of the NPY-Y1 receptor gene in PC12 cells.
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PMID:Regulation of the Y1 neuropeptide Y receptor gene expression in PC12 cells. 1140 93

Some age-related changes in immune function may be due, at least in part, to a disturbance in the communication between the nervous and immune systems. In the present work, the effects in vitro of neuropeptide Y (NPY) (10(-13) to 10(-7) M) on different peritoneal macrophage functions (adherence to substrate, chemotaxis, phagocytosis, superoxide anion production, and the release of TNFalpha and IL-1beta) have been studied on cells from young (12+/-2 weeks), adult (24+/-2 weeks), mature (50+/-2 weeks) and old (72+/-2 weeks) BALB/c mice. The specificity of these actions was confirmed using two C-terminal fragments of NPY, and the intracellular messengers (protein kinase C and cAMP) involved in the action of the neuropeptide were also analyzed. The results show that the functions studied change with aging and that the effects of NPY on each function, which are carried out through specific receptors, as well as on intracellular pathway, differ depending on age, maintaining the immune functions at physiologically adequate levels in old animals.
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PMID:Changes with aging in the modulation by neuropeptide Y of murine peritoneal macrophage functions. 1143 70

The cDNA encoding the glycoprotein alpha (GPalpha) subunit of tilapia (Oreochromis mossambicus) was partially cloned using RACE-polymerase chain reaction (PCR) technique. The amplified cDNA was found to be 583 bases long, and to consist of a portion of the signal peptide, the full sequence encoding the mature peptide (94 amino acids) and the 3' untranslated region. Northern blot analysis revealed a single band of approximately 600 bp. Alignment of the deduced amino acids of the mature protein showed that the tilapia GPalpha subunit shares more than 80% identity with that of other perciform fish (i.e. striped bass, sea bream and yellowfin porgy) and less than 70% with that of more taxonomically remote fish and other vertebrates. Exposure of dispersed tilapia pituitary cells to salmon gonadotropin-releasing hormone (sGnRH) elevated GPalpha mRNA levels via both PKC and cAMP-protein kinase A (PKA) pathways. The transcript levels were also regulated by pituitary adenylate cyclase activating polypeptide (PACAP) and neuropeptide Y (NPY), both acting through PKC and PKA pathways. Moreover, a combined treatment of PACAP or NPY with GnRH seems to have an additive effect on the GPalpha subunit gene transcription. These results suggest that in tilapia the expression of GPalpha subunit is regulated by GnRH mainly via PKC and PKA pathways. Furthermore, PACAP and NPY can elevate the GnRH-stimulated GPalpha subunit transcription and can directly affect the subunit mRNA levels, via the same transduction pathways.
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PMID:Tilapia glycoprotein hormone alpha subunit: cDNA cloning and hypothalamic regulation. 1150 Feb 38

Previous studies have demonstrated that brain-derived neurotrophic factor (BDNF) induces expression of neuropeptide Y (NPY) neurons in aggregate cultures derived from the fetal rat cortex. Using BDNF induction of NPY production and neurite extension of NPY neurons as functional and morphological criteria, respectively, we addressed the question: Does BDNF activate the extracellular-regulated kinase (ERK) pathway and if so, is activated (phosphorylated, P)-ERK required for the induction of both the functional and morphological expression of NPY? BDNF led to a rapid (30 min) and sustained (6 h) phosphorylation of ERK. PD98059 (PD, a specific inhibitor of the ERK kinase MEK), drastically inhibited, LY294002 (LY, a specific inhibitor of phosphatidylinositol-3-kinase, PI-3K) partially inhibited, and GF 109203X (GF, a specific inhibitor of protein kinase C) did not inhibit phosphorylation of ERK. A 24-h exposure to BDNF led to approximately 2-fold increase in the total culture content of NPY ( approximately 60% of which was secreted and approximately 40% remained in the aggregates) and to an abundance of neurite-bearing NPY neurons. BDNF-induced NPY produced and secreted into the medium was inhibited 73% by PD, 52% by LY and not at all by GF. In contrast, BDNF-induced NPY produced and sequestered in the aggregates was not inhibited by any of these inhibitors, suggesting a role for the ERK pathway in induced secretion of NPY. PD or LY did not inhibit BDNF-induced abundance of neurite-bearing NPY neurons. K252a (an inhibitor of TrkB-tyrosine kinase) abolished all the effects of BDNF assessed in our cultures. In summary, we demonstrate that TrkB-mediated activation of the ERK pathway is preferentially required for BDNF induction of NPY produced and secreted but not for the induction of the expression of neurite-bearing NPY neurons. Thus, BDNF induction of the functional and morphological expression of NPY is brought about by ERK-dependent and ERK-independent mechanisms.
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PMID:Induction of functional and morphological expression of neuropeptide Y (NPY) in cortical cultures by brain-derived neurotrophic factor (BDNF): evidence for a requirement for extracellular-regulated kinase (ERK)-dependent and ERK-independent mechanisms. 1168 63

Protein kinase C (PKC) activation induces neuronal differentiation of SH-SY5Y neuroblastoma cells. This study examines the role of PKCbeta isoforms in this process. The PKCbeta-specific inhibitor LY379196 had no effect on 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced neurite outgrowth from SH-SY5Y neuroblastoma cells. On the other hand, PKCbeta inhibition suppressed the TPA-stimulated increase in neuropeptide Y mRNA, activation of neuropeptide Y gene promoter elements, and phosphorylation of Erk1/2. The TPA-induced increase in neuropeptide Y expression was also inhibited by the MEK inhibitor PD98059. These data indicate that activation of a PKCbeta isoform, through a pathway involving Erk1/2, leads to increased expression of neuronal differentiation genes in neuroblastoma cells.
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PMID:A PKCbeta isoform mediates phorbol ester-induced activation of Erk1/2 and expression of neuronal differentiation genes in neuroblastoma cells. 1170 82

There is ample information on the hypophysiotropic function of pituitary adenylate cyclase-activating polypeptide (PACAP) and neuropeptide Y (NPY) in fish as in mammals, although evidence as to their direct effects on gonadotropic cells is scarce. We have previously reported that NPY and PACAP38 augment gonadotropin-releasing hormone (GnRH)-induced expression of glycoprotein alpha (alpha) subunit gene in the teleost fish, tilapia. The aim of the present study was to elucidate possible direct effects of these peptides on gonadotropin subunit gene expression in culture of tilapia pituitary cells, as well as the transduction pathways involved. Both NPY and PACAP38 (0.001-10 nM) increased the level of phosphorylated extracellular signal-regulated kinase (pERK) dose-dependently, reaching a peak at 0.1 and 0.01 nM, respectively. Inhibition of protein kinase C (PKC) by GF109203X (GF; 0.01-10 nM) suppressed NPY-stimulated pERK levels and its effect on alpha and luteinizing hormone (LH) beta subunit mRNA levels. However, NPY had no effect on follicle stimulating hormone (FSH) beta mRNA levels. NPY-elevated alpha, LHbeta mRNA and pERK levels were also attenuated by inhibition of protein kinase A (PKA) with H89 (0.01-10 nM). Exposure of the cells to the MAPK kinase (MEK) inhibitor (PD98059; PD 10, 25 and 50 microM) completely blocked NPY-induced ERK activity. In addition, this inhibitor abated the alpha and LHbeta mRNA responses to NPY. Similar experiments conducted to elucidate PACAP38 signaling revealed that PACAP38 (0.01 nM) elevated all three-gonadotropin subunit gene expression via both PKC-ERK and PKA-ERK cascades. It is suggested that both NPY and PACAP38 act directly on gonadotropes to elevate gonadotropin subunit gene expression. Whereas the expression of alpha and LHbeta subunit genes is regulated by both NPY and PACAP, the effect on the FSHbeta transcript is elicited only by PACAP38. NPY and PACAP38 stimulatory actions are mediated via protein kinase C (PKC) and protein kinase A (PKA), converging at the MEK-ERK cascade. These findings represent one of the fine tuning levels that differentially regulates gonadotropin subunit gene expression.
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PMID:Pituitary adenylate cyclase activating polypeptide and neuropeptide Y regulation of gonadotropin subunit gene expression in tilapia: role of PKC, PKA and ERK. 1191 88

1. The modulation of 4-aminopyridine sensitive transient outward potassium current (4-AP I(to)) by neuropeptide Y (NPY) (100 nM) in rat ventricular myocytes was examined using the whole cell voltage-clamp technique. 2. Continuous exposure to NPY (100 nM) for 3 - 6 h significantly increased 4-AP I(to) density. The stimulation of 4-AP I(to) density by NPY was concentration-dependent (EC(50)=10 nM). 3. In the presence of BIBP 3226, an NPY receptor antagonist that binds selectively to NPY Y1-receptors, the effect of NPY on 4-AP I(to) density was maintained. However, in the presence of BIIE 0246, a highly selective non-peptide NPY Y2-receptor antagonist, NPY was unable to increase 4-AP I(to) density. 4. The effect of NPY on 4-AP I(to) density was prevented by pretreatment with 500 ng ml(-1) pertussis toxin (PTX) and by the specific protein kinase C (PKC) inhibitor, calphostin C (100 nM). 5. Thus, short term exposure to NPY induces an increase of 4-AP I(to) density in rat ventricular myocytes mediated by Y2-receptors and involving the action of PKC via a PTX-sensitive signalling cascade.
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PMID:Neuropeptide Y increases 4-aminopyridine-sensitive transient outward potassium current in rat ventricular myocytes. 1193 10

To investigate the synergistic hypertrophic effects of neuropeptide Y (NPY) and norepinephrine (NE) and its possible signal transduction pathway on primary cardiomyocytes, neonatal cardiomyocytes were exposed to NPY, NE or angiotensin II (AnII). All three agonists induced hypertrophic effects, stimulated protein kinase C (PKC) and activated mitogen-activated protein kinase (MAPK). Moreover, NPY at sub-optimal concentration potentiated NE-, not AnII-, induced all of the above effects. Pretreatment with phorbol 12-myristate 13-acetate (PMA) completely abolished these effects for both NE and NPY. NPY potentiation was calcium-independent and pertussis toxin (PTX)-sensitive, and was different from NPY direct hypertrophic effect on cardiomyocyte, as PTX only partially abolished NPY-induced hypertrophic effects. Taken together, NPY participated in the development of cardiac hypertrophy by potentiating NE effects. The signal pathway involves PTX-sensitive G protein, PKC, MAPK, and does not require the presence of calcium.
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PMID:The signal transduction pathway causing the synergistic hypertrophic effects of neuropeptide Y and norepinephrine on primary cardiomyocyte. 1203 Aug 4

The N-terminal regions of 1-34 parathyroid hormone (PTH) and 1-34 parathyroid hormone related protein (PTHrP) are thought to be required for full agonist activity of these molecules and for signal transduction by cyclic AMP (cAMP). The C-terminal regions are thought to be involved in receptor binding and protein kinase C activation. In this study, two analogs of PTH/PTHrP lacking the segment 1-14 exhibited agonist activity in opossum kidney (OK) 3B2 cells. Analogs cPTHrP(15-34) and ANA NPY(13-36), an analog of neuropeptide Y, which both have amphipathic alpha helices, inhibited phosphate uptake and stimulated cAMP production in a dose-dependent manner, with half maximal activity in the microM range, compared to the nM range for hPTHrP(1-34) and hPTH(1-34). They also exhibited proportionately lower receptor binding affinities. cAMP production by these analogs was suppressed by the antagonist hPTHrP(7-34). Inhibition of phosphate uptake in response to the analogs was partially suppressed by H-89, but not by bisindolylmaleimide. The analogs also inhibited phosphate uptake and stimulated cAMP in parent OK cells and stimulated cAMP production in UMR-106 cells. These studies present the novel finding that in these cell types, a C-terminal region encompassing PTH/PTHrP(24-31), with the alpha-helical structure maintained, is sufficient for full activity at reduced potency.
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PMID:Bioactivity of PTH/PTHrP analogs lacking the 1-14 N-terminal domain. 1203 63

To investigate the signals governing routing of biologically active peptides to the regulated secretory pathway, we have expressed mutated and non-mutated proneuropeptide Y (ProNPY) in pituitary-derived AtT20 cells. The mutations were carried out on dibasic cleavage site and or ProNPY C-terminal sequence. Targeting to the regulated secretory pathway was studied using protein kinase A (8-BrcAMP), protein kinase C (phorbol myristate acetate) specific activators and protein synthesis inhibitor cycloheximide, and by pulse chase. The analysis of expressed peptides in cells and culture media indicated that: neuropeptide Y (NPY) and ProNPY were differently secreted, whilst NPY was exclusively secreted via regulatory pathway; ProNPY was secreted via regulated and constitutive-like secretory pathways. ProNPY secretion behaviour was not Proteolytic cleavage efficiency-dependent. The dibasic cleavage was essential for ProNPY and NPY cAMP-dependent regulated secretion and may have function as a retention signal.
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PMID:Dibasic cleavage site is required for sorting to the regulated secretory pathway for both pro- and neuropeptide Y. 1206 65


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