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)

Patients with Alzheimer's disease (AD) have been reported to have abnormalities in peripheral cells similar to some of those found in the brain, including decreased levels of protein kinase C (PKC) in fibroblasts. Since increasing evidence suggests that lithium affects PKC function, we investigated the effects of 3 weeks of lithium administration on the immunolabeling of 4 PKC isozymes (alpha, beta, epsilon, and zeta) in particulate and soluble fractions from platelets of 7 patients with probable AD and 6 age-matched controls. AD patients had significantly less particulate or membrane-associated PKC zeta than normals during the placebo phase (P < 0.003). After 3 weeks of lithium treatment, AD patients had significantly less membrane-associated PKC alpha (P < 0.002), epsilon (P < 0.003), and zeta (P < 0.001) than normals. This is the first report of a difference in PKC in blood cells between AD and control subjects. These findings appear to indicate that some PKC isozymes may be differentially regulated in AD versus elderly controls, at least as evidenced in this peripheral cellular system.
 ...
PMID:Effects of chronic lithium treatment on platelet PKC isozymes in Alzheimer's and elderly control subjects. 812 26

The phorbol ester binding domain consists of a cysteine-rich region with a postulated consensus sequence for binding that includes 15 amino acids (Ahmed, S., Kozma, R., Lee, J., Monfries, C., Harden, N., and Lim, L. (1991) Biochem. J. 280, 233-241). In PKC zeta, the only PKC isoform lacking phorbol ester binding, this region differs in a single residue from the consensus (proline in position 11 of the motif). Restoration of this proline by site-directed mutagenesis of PKC zeta does not restore binding of either [3H]phorbol 12,13-dibutyrate or of the ultrapotent ligand [3H]bryostatin 1, suggesting that even a low affinity ligand interaction is absent. In addition, the vav and c-raf proto-oncogene products, proteins that possess cysteine-rich regions with high homology to PKC isozymes and other phorbol ester receptors, are unable to bind any of these ligands. Instead, all of these cysteine-rich regions bind zinc. Our results suggest that other amino acids besides those postulated for the consensus must be necessary for ligand binding and argue against direct modulation of PKC zeta, Vav, and c-Raf by phorbol esters.
 ...
PMID:Zinc finger domains and phorbol ester pharmacophore. Analysis of binding to mutated form of protein kinase C zeta and the vav and c-raf proto-oncogene products. 815 92

Adenocarcinoma of the prostate is the second leading cause of cancer deaths in men. The protein kinase C (PKC) family of signal transducing kinases has been implicated in neoplastic transformation and progression in other tissues, and some evidence suggests roles for PKC in prostate growth and neoplasia. We have detected expression of eight specific PKC isozyme mRNAs (alpha, beta, gamma, delta, epsilon, eta, theta, and zeta) in normal rat whole prostate and found some of these to be differentially expressed in certain Dunning R-3327 rat prostatic adenocarcinoma sublines. PKC zeta mRNA was detected in normal prostate and Dunning H tumor, whereas an alternatively spliced form of PKC zeta RNA was found in Dunning G tumor and normal brain. Both forms of PKC zeta RNA were markedly reduced in the androgen insensitive, highly metastatic Dunning AT-3, MAT-Lu, and MAT-LyLu tumors. We have cloned and report the sequence of the novel portion of the alternatively spliced form of PKC zeta RNA, which is polyadenylated and present in cytoplasm.
 ...
PMID:Differential expression of protein kinase C isozyme messenger RNAs in dunning R-3327 rat prostatic tumors. 818 Jan 27

We have studied the PKC isoforms present in HT-29 M6 colon cancer cells, the differentiation of which to mucus-secreting cells is blocked by TPA. In addition to a major 72 kDa band, a 77 kDa PKC isoform was recognized by two different antibodies raised against a C-terminus-specific peptide for the TPA-insensitive isoform, PKC zeta. By different criteria (association to the membrane, down-regulation, PKC activity in immunoprecipitates) we conclude that, contrary to the 72 kDa band, the 77 kDa band corresponds to a Ca(2+)- and TPA-sensitive PKC. These results suggest that antipeptide antibodies directed against the C-terminus of PKC zeta react in human cells with a member of the conventional PKC subfamily besides PKC zeta. Therefore, the data indicating that PKC zeta is sensitive to different agents in various cell lines should be carefully re-evaluated.
 ...
PMID:Antipeptide antibodies directed against the C-terminus of protein kinase C zeta (PKC zeta) react with a Ca(2+)- and TPA-sensitive PKC in HT-29 human intestinal epithelial cells. 818 76

We have utilized several peptide specific antisera directed against the C-terminals (Wetsel et al, 1992) of several protein kinase C (PKC) isozymes (alpha, beta 1, beta 11, gamma, delta, epsilon, zeta) to delineate the cellular localization of these PKC isozymes in rat retina. Antisera against PKC beta 1, beta 11, gamma, delta and epsilon were non-reactive in frozen rat retina sections, whereas, anti PKC alpha was strongly reactive with the outer plexiform, inner plexiform and nerve fiber cell layers. The most specific localization of immunoreactivity was observed with PKC zeta, which reacted strongly and exclusively with photoreceptor inner segments, but not outer segments. Immunoblot analysis of whole rat retina homogenate showed that anti-PKC alpha recognized an antigen of approximately 80kD and anti-PKC zeta recognized a approximately 72kD protein. Immunolocalization of PKC zeta to photoreceptor inner segments and possible functional significance are discussed.
 ...
PMID:Immunolocalization of PKC zeta in rat photoreceptor inner segments. 819 61

Cyclic AMP production within cells is altered upon protein kinase C (PKC) activation; however, whether PKC directly modulates adenylyl cyclase (AC) catalytic activity has been controversial. Molecular studies have elucidated the existence of multiple PKC isoenzymes although the functional role of this diversity is not clear. Using purified PKC and AC isoenzymes, we demonstrate that PKC zeta directly phosphorylates type VAC, leading to an approximate 20-fold increase in its catalytic activity, a significantly larger enhancement than that achieved with forskolin (approximately 5-fold), the most potent activator of AC. When forskolin and PKC phosphorylation are combined, type V AC catalytic activity is increased 100-fold over basal levels. The two PKC isoenzymes (alpha and zeta) are additive in their capacity to activate AC, although PKC alpha is less potent than PKC zeta. Our data indicate that PKC can directly and potently regulate AC activity in an isoenzyme-specific manner, suggesting that direct cross-talk plays a major role in coordinating the activity of these two principal signal transduction pathways.
 ...
PMID:Differential activation of adenylyl cyclase by protein kinase C isoenzymes. 820 71

We have immunologically identified the isoforms of protein kinase C (PKC) present in neonatal and adult rat cardiomyocytes and examined their regulation by hormones and phorbol ester. Both cell types express the Ca(2+)-dependent alpha-PKC and the Ca(2+)-independent epsilon- and delta-PKC isoforms. The atypical zeta-PKC isoform is also expressed in neonatal, but only weakly in adult cells. Stimulation of the alpha 1-adrenergic or purinergic receptor with phenylephrine or ATP, respectively, increases membrane-associated immunoreactivity of both epsilon- and delta-PKC in neonatal and adult cells; endothelin and carbachol are also effective in adult cells. In contrast, none of the agonists leads to increases in membrane-associated alpha-PKC in cardiomyocytes. PKC zeta is also unaffected by receptor stimulation. The phorbol ester phorbol 12-myristate 13-acetate causes redistribution and subsequently down-regulation of alpha-, epsilon-, and delta- but not zeta-PKC. The three isoforms are down-regulated at distinctively different rates, with alpha-PKC being the most rapid and epsilon-PKC the slowest. We used selective down-regulation of alpha-, epsilon-, and delta-PKC to investigate the role of these isoforms in PKC phosphorylation-dependent events in neonatal myocytes. Our findings suggest that epsilon-PKC is responsible for the phenylephrine-induced phosphorylation of MARCKS, an endogenous PKC-specific substrate. In contrast, agonist-induced c-fos expression is unlikely to be mediated by epsilon-PKC since the response is rapidly down-regulated and apparently Ca(2+)-dependent. Our finding that the PKC isoforms are differentially responsive to neurohormones suggests that they play distinct and specific roles in cardiac function.
 ...
PMID:Differential regulation of protein kinase C isoforms in isolated neonatal and adult rat cardiomyocytes. 820 17

Induction of erythroid differentiation of murine erythroleukemia cells (MELC) by exposure to hexamethylene bisacetamide (HMBA) involves the modulation of protein kinase C (PKC) activity. Using immuno- and Northern blot techniques, we have demonstrated that MELC express a pattern of PKC isoforms which includes PKC alpha, PKC delta, PKC epsilon, PKC zeta, and PKC eta. We show that MELC resistant to induction by HMBA express significantly less of the nPKC isoform, PKC delta, and slightly less PKC epsilon. Recovery of HMBA sensitivity is associated with reexpression of PKC delta protein. Upon exposure to HMBA, there is a fall in cytosolic PKC delta and PKC epsilon accompanied by a transient increase in membrane-associated forms of these PKC isoforms. HMBA-resistant MELC fail to display this isoform-specific translocation of PKC. Induction of differentiation is accompanied, over the next 24 h of exposure to HMBA, by a progressive fall in cellular PKC activity, associated with a progressive fall in the cellular content of PKC delta, PKC epsilon, and PKC zeta. These studies suggest that PKC delta, and possibly PKC epsilon and PKC zeta as well, play a role in the pathway of HMBA-mediated terminal cell differentiation of MELC.
 ...
PMID:Differential modulation of protein kinase C isoforms in erythroleukemia during induced differentiation. 822 97

The protein kinase C (PKC) family of serine-threonine kinases comprises at least eight members. These are differentially expressed, show varying affinities for activators such as Ca2+ and lipid species, and are therefore thought to play wide-ranging roles in the regulation of such cellular processes as differentiation, growth, and secretion. The aim of this study was to identify new PKC isoforms in the insulin-secreting cell line RINm5F that might be activated by the alterations in lipid metabolism that accompany nutrient-stimulated insulin release. Fragments of cDNA, derived from RINm5F cell mRNA, were amplified by the polymerase chain reaction using degenerate oligonucleotide primers corresponding to highly conserved regions in the catalytic domains of all known PKCs. A novel sequence generated by this approach was subsequently used to screen cDNA libraries. The entire 587-amino acid coding region of a new PKC isoform, PKC iota, was deduced from two overlapping clones isolated from a human kidney cDNA library. The amino acid sequence of PKC iota showed greatest homology to PKC zeta, with 72% identity overall rising to 84% in the catalytic domain. In contrast, the homology of PKC iota to the other isoforms was less pronounced, with < 53% identity even in the highly conserved catalytic region. Further similarities between PKC zeta and PKC iota included a highly conserved pseudosubstrate sequence, the absence of an apparent Ca(2+)-binding region, and the presence of only one cysteine-rich, zinc finger-like domain. Northern blot analysis, using the full-length PKC iota clone as a probe, revealed a single 4.6-kilobase transcript present predominantly in lung and brain, but also expressed at lower levels in many tissues including pancreatic islets. In CHO-K1 cells stably expressing the PKC iota cDNA under the human beta-actin promoter, the protein was detected as a 65-kDa band by Western blotting using an antibody to the COOH terminus of PKC zeta (conserved in PKC iota). Extracts of transfected CHO-K1 cells also displayed a significantly increased kinase activity using myelin basic protein as a substrate. The results suggest that PKC iota should be included in the atypical subgroup of PKCs whose definitive member is PKC zeta. As such, PKC iota is unlikely to be activated by the diacylglycerol that is derived from phosphoinositide hydrolysis, but might be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion.
 ...
PMID:Molecular cloning and characterization of PKC iota, an atypical isoform of protein kinase C derived from insulin-secreting cells. 822 78

The goal of this study was to compare the response of mouse epidermal keratinocytes (MEKs) and human epidermal keratinocytes (HEKs) to 12-O-tetradecanoylphorbol-13-acetate (TPA) with respect to the activation and downregulation of protein kinase C (PKC), the expression of c-jun and c-fos, and the expression and induction of ornithine decarboxylase (ODC) activity. Keratinocytes from adult CD-1 mice and from discarded adult human skin were grown in primary culture in a high-calcium serum-free medium that supported proliferation and differentiation. Immunoblotting of freshly isolated and cultured MEKs and HEKs for isozymes of protein kinase C revealed that fresh HEKs contained PKC alpha, PKC beta, and PKC delta; no PKC gamma, PKC epsilon, or PKC zeta were detected. In fresh MEKs, PKC alpha, PKC beta, PKC delta, and PKC zeta were observed, but not PKC gamma or PKC epsilon. After 2 wk in culture, the isozyme profiles of MEKs and HEKs were similar except that PKC gamma was noticeably present in HEK cultures. Activation of partially purified total PKC by TPA was similar in freshly isolated and cultured MEKs and HEKs, indicating that the two species were similar in this regard and that 2 wk of culture did not alter this characteristic. When MEK and HEK cultures were treated with TPA for 3 h, less than 30% of the control level of PKC activity was detected, indicating that TPA-induced downregulation of PKC was similar in MEKs and HEKs. After treatment with TPA, MEK cultures produced a large induction of both c-jun and c-fos mRNA by 60 min, as determined by northern blot analysis, and a large induction of ODC mRNA and enzyme activity by 6 h. TPA treatment of cultured HEKs, however, did not induce ODC activity; in fact, less activity, compared with that of control cultures, was observed. Northern blot analysis also revealed no increase in c-jun, c-fos, and ODC mRNA in HEKs. However, c-jun and c-fos mRNA and both ODC mRNA and enzyme activity were induced in HEKs fed growth factors after several days of deprivation. This suggests that the lack of ODC induction by TPA in HEKs is probably due to species differences in downstream steps in PKC signal transduction.
 ...
PMID:Association of protein kinase C activation with induction of ornithine decarboxylase in murine but not human keratinocyte cultures. 835 82


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