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

Prenatal ethanol exposure can cause a number of physiological deficits known as fetal alcohol syndrome (FAS). Because protein kinase C (PKC) regulates the cell cycle and has been linked to growth, we examined the effect of ethanol on PKC isoform expression in a developing chick brain. Ethanol exposure causes decreased head weight in chickens at day 5 in a dose-dependent manner and a decreased brain weight at days 7 and 10 at an ethanol concentration of 1.0 g/kg. Antibodies specific for PKC-alpha, beta, gamma, delta, epsilon, iota, lambda, mu and zeta were used to examine ethanol's effect on PKC expression in the growth-suppressed brain at days 5, 7 and 10 of development. Only four of the PKC isoforms tested are expressed in the chick brain prior to day 10: alpha, gamma, epsilon, and iota. PKC-alpha, gamma, and epsilon are developmentally increased during the time period studied. Ethanol causes a decreased expression of PKC-alpha on days 5, 7 and 10 and a decreased expression of PKC-gamma on days 7 and 10. Ethanol causes a decreased expression of PKC-epsilon only on day 7. PKC-iota expression is unchanged over the developmental times studied and ethanol exposure has no effect on PKC-iota expression. These data suggest that only specific PKC isoforms are developmentally expressed in the embryonic chick brain and that ethanol may inhibit the expression of those PKC isoforms that are developmentally regulated.
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PMID:Ethanol-induced decrease of developmental PKC isoform expression in the embryonic chick brain. 1056 37

In the present study, we investigated the expression of mRNA of protein kinase C (PKC) isoenzymes (alpha, beta, gamma, delta, epsilon, zeta, eta, and theta) in normal (+/+) and W mutant alleles mice testes. In +/+ mice testes, abundant expression of PKCdelta and PKCtheta was observed, while other PKCs (alpha, beta, gamma, epsilon, zeta, and eta) generally were not detected by Northern blotting. The PKCdelta and PKCtheta isoenzymes demonstrated a distinctive cellular distribution when evaluated by in situ hybridization. We have previously shown that PKCdelta gene was selectively expressed in spermatid of +/+ testes. Here we show that PKCdelta gene is also present in spermatid of Wsh/Wsh mice testes and PKCtheta gene was present in interstitial cells of +/+, Wsh/Wsh, and W/Wv mice testes. These studies provide the evidence of selective cell distributions of the PKC isoenzymes and suggest that PKC has the functional significance in testes.
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PMID:Expression of protein kinase C genes in normal (+/+) and W mutant alleles (Wsh/Wsh, W/Wv) mice testes. 1073 59

The aim of the present study was to assess the status of ET-1 receptor subtypes (ET(A)and ET(B)) in ventricular myocytes and fibroblasts and to determine the role of PKC-dependent pathways in ET-1-stimulated cardiac cells in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Systolic blood pressure and relative heart to body weight were significantly increased in DOCA-salt rats. In unilaterally nephrectomized (Uni-Nx) control rats, more than 90% of cardiomyocyte ET receptors were of the ET(A)subtype, whereas in fibroblasts ET(A)and ET(B)receptors were present in a 1:3 ratio. In DOCA-salt rats, the density of the ET(A)receptor subtype was reduced by 31% in cardiomyocytes and in cardiac fibroblasts only ET(B)receptor density was decreased by 29%. Affinity was unchanged. The relative expression of immunoreactive PKC alpha, gamma and epsilon was significantly increased, whereas PKC delta was not altered in cardiac extracts of DOCA-salt rats. In cardiac fibroblasts from DOCA-salt rats PKC delta was significantly increased and PKC epsilon was not translocated after ET-1 stimulation. The hearts of DOCA-salt hypertensive rats are thus characterized by: (1) decreased density of cardiomyocyte ET(A)receptors and fibroblast ET(B)receptors; (2) cell-specific enhanced expression of some PKC isoenzymes (alpha, gamma, delta and epsilon); and (3) unresponsiveness of PKC epsilon to translocate in the presence of ET-1. Together with alterations of ET-1-induced Ca(2+)handling in cardiac myocytes and fibroblasts, which we previously reported, results from the present study indicate a marked modification of the cardiac ET-1 system of DOCA-salt hypertensive rats.
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PMID:Altered cardiac endothelin receptors and protein kinase C in deoxycorticosterone-salt hypertensive rats. 1075 22

Physiological vasoconstrictor concentrations of Arg8-vasopressin (AVP, 10-100 pM) stimulate oscillations (spikes) in cytosolic free Ca2+ concentration ([Ca2+]i) in A7r5 rat vascular smooth muscle cells. These Ca2+ spikes are dependent on L-type voltage-sensitive Ca2+ channels and increase in frequency with increasing AVP concentration. The signal transduction pathway responsible for this effect was examined in fura-2-loaded A7r5 cell monolayers. The serine/threonine phosphatase inhibitor calyculin A (5 nM) sensitized A7r5 cells to AVP, resulting in the stimulation of Ca2+ spiking by 1-10 pM AVP. Calyculin A alone did not stimulate Ca2+ spiking. The protein kinase C (PKC) activator 4beta-phorbol 12-myristate 13-acetate (PMA, 100 pM to 200 nM), also stimulated Ca2+ spiking and this effect was additive with a submaximal concentration of AVP (50 pM). The PKC inhibitors Ro-31-8220 (1 microM) and calphostin C (250 nM) completely blocked the stimulation of Ca2+ spiking by either PMA or AVP. alpha, beta, gamma, delta, epsilon, zeta and &lamdda; isoforms of PKC were detected in A7r5 cells by Western blot analysis. Time-dependent redistribution of PKC-alpha, -delta and -epsilon isoforms between the membrane and cytosolic fractions occurred in response to 100 pM AVP. Pretreatment for 24 h with 1 microM PMA downregulated expression of PKC-alpha and -delta, but not PKC-epsilon, and prevented the Ca2+-spiking responses to either 1 nM PMA or 100 pM AVP. Neither the release of intracellular Ca2+ by 1 microM AVP nor the increase in [Ca2+]i in response to elevated extracellular [K+] was prevented by the PMA pretreatment. We conclude that PKC activation is a necessary step in the signal transduction pathway linking low concentrations of AVP to Ca2+ spiking in A7r5 cells.
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PMID:Ca2+ signalling in rat vascular smooth muscle cells: a role for protein kinase C at physiological vasoconstrictor concentrations of vasopressin. 1079 Jan 61

We examined the modulation of protein kinase C (PKC) subtypes during apoptosis induced by ginsenoside Rh2 (G-Rh2) in human neuroblastoma SK-N-BE(2) and rat glioma C6Bu-1 cells. Apoptosis induced by G-Rh2 in both cell lines was confirmed, as indicated by DNA fragmentation and in situ strand breaks, and characteristic morphological changes. During apoptosis induced by G-Rh2 in SK-N-BE(2) cells, PKC subtypes alpha, beta and gamma were progressively increased with prolonged treatment, whereas PKC delta increased transiently at 3 and 6 h and PKC epsilon was gradually down-regulated after 6 h following the treatment. On the other hand, PKC subtype zeta markedly increased at 24 h when maximal apoptosis was achieved. In C6Bu-1 cells, no significant changes in PKC subtypes alpha, gamma, delta, epsilon and zeta were observed during apoptosis induced by G-Rh2. These results suggest the evidence for a possible role of PKC subtype in apoptosis induced by G-Rh2 in SK-N-BE(2) cells but not in C6Bu-1 cells, and raise the possibility that G-Rh2 may induce apoptosis via different pathways interacting with or without PKC in different cell types.
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PMID:Differential expression of protein kinase C subtypes during ginsenoside Rh2-lnduced apoptosis in SK-N-BE(2) and C6Bu-1 cells. 1105 34

Halogenated aromatic hydrocarbon including polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental toxicants. Although health effects associated with exposure to these chemicals, including motor dysfunction and impairment in memory and learning, have been identified, their molecular site of action is unknown. Previous study from this laboratory demonstrated that, while ortho PCBs perturbed intracellular signaling mechanisms including Ca2+ homeostasis, receptor-mediated inositol phosphate production and translocation of PKC, non-ortho PCBs did not. Since PKC signaling pathway is implicated in the modulation of motor behavior, as well as learning and memory, and the roles of PKC are isoform-specific, we have now studied the effects of two structurally distinct PCBs on isoforms of PKC in cerebellar granule cell culture model. Cells were exposed to 2,2'-dichlorobiphenyl (ortho PCB; 2,2'-DCB) or 4,4'-dichlorobiphenyl (non-ortho PCB; 4,4'-DCB) for 15 min, respectively, and subsequently fractionated and immunoblotted against the selected PKC monoclonal antibodies (alpha, gamma, delta, epsilon, lambda, iota). While 2,2'-DCB induced a translocation of PKC-alpha [cytosol (% control): 54 +/- 12 at 25 microM and 66 +/- 10 at 50 microM; membrane (% control): 186 +/- 37 at 25 microM and 200 +/- 48 at 50 microM] and -epsilon [cytosol (% control): 92 +/- 12 at 25 microM and 97 +/- 15 at 50 microM; membrane (% control): 143 +/- 23 at 25 microM and 192 +/- 24 at 50 microM] from cytosol to membrane fraction in a concentration-dependent manner, 4,4'-DCB had no effects. 2,2'-DCB induced translocation of PKC-alpha was blocked by pretreatment with sphingosine, suggesting a possible role of sphingolipid pathway. Although reports on implication of PKC-gamma with learning and memory are relatively extensive, the expression of this particular isoform in the primary cerebellar granule cells was below the detectable level. PKC-delta, -lambda and -iota were present in these cells, but were not altered by PCB exposure. These results suggest that the effects of 2,2'-DCB on PKC is isoform-dependent and PKC-alpha as well as PKC-epsilon may be target molecules for ortho-PCBs in neuronal cells.
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PMID:Possible molecular targets of halogenated aromatic hydrocarbons in neuronal cells. 1116 82

Integrin alpha 3A cytoplasmic tail phosphorylation was mapped to amino acid S1042, as determined by mass spectrometry, and confirmed by mutagenesis. This residue occurs within a "QPSXXE" motif conserved in multiple alpha chains (alpha 3A, alpha 6A, alpha 7A), from multiple species. Phosphorylation of alpha 3A and alpha 6A did not appear to be directly mediated by protein kinase C (PKC) alpha, beta, gamma, delta, epsilon, zeta, or mu, or by any of several other known serine kinases, although PKC has an indirect role in promoting phosphorylation. A S1042A mutation did not affect alpha 3-Chinese hamster ovary (CHO) cell adhesion to laminin-5, but did alter 1) alpha 3-dependent tyrosine phosphorylation of focal adhesion kinase and paxillin (in the presence or absence of phorbol 12-myristate 13 acetate stimulation), and p130(CAS) (in the absence of phorbol 12-myristate 13 acetate stimulation), 2) the shape of cells spread on laminin-5, and 3) alpha 3-dependent random CHO cell migration on laminin-5. In addition, S1042A mutation altered the PKC-dependent, ligand-dependent subcellular distribution of alpha 3 and F-actin in CHO cells. Together, the results demonstrate clearly that alpha 3A phosphorylation is functionally relevant. In addition, the results strongly suggest that alpha 3 phosphorylation may regulate alpha 3 integrin interaction with the cytoskeleton.
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PMID:Phosphorylation of a conserved integrin alpha 3 QPSXXE motif regulates signaling, motility, and cytoskeletal engagement. 1117 20

In the eel, angiotensin II (Ang II) has a role at the level of both gill chloride and kidney tubular cells, regulating sodium balance and therefore osmoregulation. The present study extends these findings to another important osmoregulatory organ - the intestine. Enterocytes were obtained from sea-water (SW)-acclimated eels to investigate the role of Ang II on the intestinal Na+/K+ATPase activity, because in SW-acclimated animals the intestine represents an important site of water and NaCl transport from the mucosal to the serosal side. This paper demonstrates that isolated enterocytes stimulated with increasing Ang II concentrations (0.01-100 nM) showed a dose-dependent inhibition of the Na+/K+ATPase activity. The threshold decrease was at 0.01 nM Ang II; it reached a maximum at 10 nM (81.5% inhibition) and did not decrease further with the use of higher hormone doses. These hormonal effects were blocked by a specific competitive antagonist of the AT1 receptor subtype, DuP-753 (100% inhibition at 10 microM), indicating that these effects are mediated by an AT1-like receptor. Isolated enterocytes stimulated with 10 nM Ang II showed a transient increase in intracellular calcium ([Ca2+]i), followed by a lower sustained phase. Removal of extracellular Ca2+ did not reduce the initial transient response and completely abolished the plateau phase. The inhibition of the Na+/K+ATPase activity was dependent on protein kinase C (PKC) activation since PKC antagonists (calphostin C and staurosporine) abolished the inhibitory effect of Ang II, and the PKC activator phorbol 12-myristate 13-acetate reduced transporter activity. Western blot analysis with antibodies to PKC alpha, beta I, beta II, gamma, delta, epsilon, iota, eta and zeta isoforms showed that eel enterocytes expressed the conventional isoforms (alpha and beta I), the novel isoforms (delta and eta) and the atypical isoforms (zeta and iota). Ang II stimulated the translocation from the cytosol to the plasma membrane of PKC alpha, PKC delta and PKC eta isoforms. In conclusion, our results suggest that Ang II modulates intestinal Na+/K+ATPase in SW-acclimated eels via calcium mobilization and PKC activation.
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PMID:Na+/K+ATPase activity inhibition and isoform-specific translocation of protein kinase C following angiotensin II administration in isolated eel enterocytes. 1118 72

Evidence is provided for direct protein-protein interactions between protein kinase C (PKC) alpha, betaI, betaII, gamma, delta, epsilon, and zeta and members of the Rho family of small GTPases. Previous investigations, based on the immunoprecipitation approach, have provided evidence consistent with a direct interaction, but this remained to be proven. In the study presented here, an in vitro assay, consisting only of purified proteins and the requisite PKC activators and cofactors, was used to determine the effects of Rho GTPases on the activities of the different PKC isoforms. It was found that the activity of PKCalpha was potently enhanced by RhoA and Cdc42 and to a lesser extent by Rac1, whereas the effects on the activities of PKCbetaI, -betaII, -gamma, -delta, -epsilon, and -zeta were much reduced. These results indicate a direct interaction between PKCalpha and each of the Rho GTPases. However, the Rho GTPase concentration dependencies for the potentiating effects on PKCalpha activity differed for each Rho GTPase and were in the following order: RhoA > Cdc42 > Rac1. PKCalpha was activated in a phorbol ester- and Ca(2+)-dependent manner. This was reflected by a substantial decrease in the phorbol ester concentration requirements for activity in the presence of Ca(2+), which for each Rho GTPase was induced within a low nanomolar phorbol ester concentration range. The activity of PKCalpha also was found to be dependent on the nature of the GTP- or GDP-bound state of the Rho GTPases, suggesting that the interaction may be regulated by conformational changes in both PKCalpha and Rho GTPases. Such an interaction could result in significant cross-talk between the distinct pathways regulated by these two signaling elements.
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PMID:Interaction of protein kinase C isozymes with Rho GTPases. 1128

The role of the different isoforms of protein kinase C (PKC) in modulating insulin secretion is still widely unknown. The aim of our studies was to investigate which isoforms are influenced by gastrin-releasing peptide (GRP), a neuropeptide which has been shown to modulate insulin secretion by activating PKC. Presence of PKC isoforms alpha, beta, gamma, delta, epsilon and zeta was tested by immunoblot analysis in whole pancreatic islets of mouse and rat and in the insulinoma cell line RINm5F. Effects of GRP, the truncated peptide GRP1-16 and KCl were also measured on translocation of PKC isoforms. In pancreatic islets of mouse and rat, the PKC isoforms alpha, beta, gamma, delta, epsilon and zeta could be detected. No PKCgamma activity was present in the pancreatic tumor cell line RINm5F. Incubation of mouse or rat islets or of RINm5F cells with GRP induced translocation of the PKC isoforms alpha, beta and zeta. The N-terminal portion of the peptide GRP1-16 induced partial translocation only of the PKC isoforms alpha, beta and zeta in mouse and rat islets in 4 out of 10 cases, but failed to show any effect on PKC isoforms in RINm5F cells. Depolarization of the islets by KCl did not translocate any tested PKC isoform. However, incubation with GRP followed by depolarization with KCl led to translocation of the PKC isoforms alpha, beta and zeta. It is suggested that PKC alpha, beta and/or zeta may play a role in the modulation of insulin secretion by GRP.
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PMID:Distribution and stimulation by gastrin-releasing peptide of protein kinase C subfamilies in insulin-secreting cells. 1139 8


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