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 extension of cellular processes from the oligodendrocyte soma is an early and critical event in myelin formation. Previous reports from this laboratory have implicated a role for protein kinase C (PKC) as an important intracellular mediator of this critical step in myelinogenesis. In the current study, the regrowth of fibers by adult human oligodendrocytes was examined and was found to be significantly enhanced by the PKC stimulator, 4 beta-phorbol-12,13-didecanoate (PDB); this was accompanied by a 400-500% increase in oligodendroglial PKC activity. In contrast to other cell types, the increased PKC activity in oligodendrocytes was not followed by subsequent down-regulation of the enzyme. The role of PKC in oligodendroglial process formation was further demonstrated by the ability of inhibitors of PKC to block the basal- or PDB-enhanced fiber outgrowth. As well, studies employing isoform-specific agonists implicated PKC alpha as the major determinant of fiber outgrowth by oligodendrocytes. The potential significance of PKC in myelin formation was further underscored by the observation that the synthesis of myelin basic protein, a prerequisite component for myelinogenesis, was increased by 2-fold in PDB-treated oligodendrocytes. Collectively, these observations suggest that PKC, in particular the alpha isoform, constitutes an important mediator in the initiation of myelin formation.
 ...
PMID:Protein kinase C in cultured adult human oligodendrocytes: a potential role for isoform alpha as a mediator of process outgrowth. 780 94

To investigate the role of protein kinase C (PKC) in the growth of astrocytic brain tumors, human glioblastoma cell line U-87 was stably transfected with the antisense complementary deoxyribonucleic acid encoding PKC alpha. The effect of selectively down-regulating the alpha isoform on other PKC isoforms, as well as serum-dependent proliferation and in vivo tumorigenicity, was determined. U-87 cells expressed high levels of PKC alpha and lesser amounts of the gamma, epsilon, and zeta isoforms, and a similar PKC isoform pattern was observed in two other human glioblastoma cell lines. Expression of the antisense PKC alpha complementary deoxyribonucleic acid resulted in no detectable PKC alpha by immunoblotting and a 95% reduction in total Ca2+/phospholipid-dependent PKC activity. U-87 cells expressing antisense PKC alpha exhibited an increase in doubling time in vitro, less serum-dependent growth, and reduced sensitivity to a selective PKC inhibitor, Ro 31-8220. The transplantation of U-87 cells expressing antisense PKC alpha into nude mice resulted in no tumor formation. These observations suggest that the inhibition of PKC alpha may be an important chemotherapeutic target for arresting the growth of glioblastomas.
 ...
PMID:Antisense expression of protein kinase C alpha inhibits the growth and tumorigenicity of human glioblastoma cells. 783 40

Following LTP induction in freely moving rats, in situ hybridization revealed discrete changes in the expression of one isoform in each of four families of serine/threonine kinases constitutively expressed in the dentate gyrus of the hippocampus. Expression of the alpha isoform of CaMKII showed a transient increase over the soma and a more persistent increase over the dendritic field of dentate granule cells. Of the PKC isoforms, only gamma PKC was up-regulated substantially 2 hr after LTP induction, declining to control levels 48 hr later. An increase in the expression of mRNA for ERK2 and raf-B was seen at 24 hr only. These results show that, during the maintenance phase of LTP in the hippocampus, there are selective increases in the expression of serine/threonine kinases and that these increases have specific and characteristic temporal and spatial profiles.
 ...
PMID:Spatial and temporal changes in signal transduction pathways during LTP. 791 3

The activity and expression of Ca(2+)-dependent cPKC alpha and beta isoenzymes in the particulate, soluble (cytosolic) and nuclear fractions of rat liver and the expression of Ca(2+)-independent nPKC delta and aPKC zeta were examined during the early stages (30 and 60 min, 24 and 96 h and 7 and 60 days post-hepatectomy) of the Solt-Farber 'resistant hepatocyte' model of diethylnitrosamine (DENA)-induced hepatocarcinogenesis in Fischer 344 rats and related to the presence of gamma-glutamyl transpeptidase (GGT)-positive hyperplastic cell foci and persistent nodules in rat liver. Total PKC activity was unmodified by the carcinogenic treatment. In contrast, the PKC activity in the particulate, as well as nuclear fractions increased with time, reaching a maximum 60 days post-hepatectomy, with a decrease in the cytosolic activity. In carcinogen-treated animals maximal expression of cPKC alpha and beta isoenzymes was present 7 days post-hepatectomy, while no changes in nPKC delta and aPKC zeta immunoreactivity were detected. In the nucleus, no cPKC alpha isoform expression was observed, the cPKC beta expression being maximal at 60 days. Seven and 60 days post-hepatectomy GGT-positive hyperplastic cell foci and persistent nodules were present in rat liver respectively. Taken together, the results of this study suggest a role for nuclear cPKC beta and for cPKC alpha in promoting the selective growth of carcinogen-initiated hepatocytes in rat liver. No evidence for a role of Ca(2+)-independent nPKC delta and aPKC zeta isoenzymes in the early stages of DENA-induced liver carcinogenesis could be demonstrated.
 ...
PMID:Membrane and nuclear protein kinase C activation in the early stages of diethylnitrosamine-induced rat hepatocarcinogenesis. 805 57

Protein kinase C activity was detected in the cytosolic fraction of quiescent parotid acinar cells; the particulate fraction contained a much smaller proportion of the enzyme. Protein kinase C activity was increased in the membrane fraction and decreased in the cytosol after exposure of intact cells to phorbol 12-myristate 13-acetate (PMA) or the muscarinic-receptor agonist carbachol. The effect of PMA was potentiated by a subthreshold concentration of ionomycin. Immunoblot analysis with anti-protein kinase C antibodies revealed that the protein kinase C-alpha isoform is expressed in rat parotid cells. Other Ca(2+)-dependent isoforms were not detected. Further, agonist stimulation caused the redistribution of protein kinase C-alpha from cytosol to a membrane fraction. Agonists may promote parotid acinar cell activity, including amylase secretion, by increasing the affinity of protein kinase C-alpha for the membrane fraction, presumably via a rise in Ca2+ and diacylglycerol derived from polyphosphoinositide hydrolysis.
 ...
PMID:Translocation of the alpha-isozyme of protein kinase C during stimulation of rat parotid acinar cells by phorbol ester and carbachol. 814 66

A partial cDNA sequence indicated that the T lymphocyte early-activation gene (Tea) encodes a protein related to the dual-function ecotropic retrovirus receptor/cationic amino acid transporter (ecoR/CAT1), and RNA blots suggested highest Tea expression in T lymphocytes and liver (MacLeod, C.L., Finley, K., Kakuda, D. Kozad, C.A., and Wilkinson, M.F. (1990) Mol. Cell. Biol. 7, 3663-3674). The sequence of full-length Tea cDNA from liver (3683 bases) predicts a 657-amino-acid protein (CAT2 alpha) with 12-14 transmembrane domains. A long (515 base) region with six initiation codons and termination codons precedes the translation start codon. The liver Tea cDNA is identical to Tea cDNA from T lymphocytes (encoding CAT2 beta) with the exception of an apparent alternatively spliced sequence encoding a hydrophilic loop of 43 amino acids. The liver-specific sequence contains unique consensus sites for phosphorylation by cyclic AMP-dependent protein kinase and by protein kinase C. Injection of Xenopus oocytes with CAT2 alpha or CAT2 beta messenger RNA resulted in expression of Na(+)-independent cationic amino acid transport that was detected by current measurements under voltage-clamp. Although the amino acid sequences of the isoforms differ in only 21 of 43 residues with the majority of substitutions being conservative, the apparent affinity of CAT2 beta for arginine uptake was 70-fold higher than the CAT2 alpha isoform (Km 38 microM versus 2.7 mM). Neither isoform functioned as a receptor for ecotropic or amphotropic murine retroviruses. However, CAT1-CAT2 chimeric proteins that contain the first three putative extracellular loops of ecoR/CAT1 functioned as ecotropic receptors despite a diminished capacity to bind the viral envelope glycoprotein. The chimeric proteins also functioned as basic amino acid transporters with substrate affinities corresponding to the CAT2 isoform constituting the carboxyl-terminal portion. These results demonstrate that domains of these transporters can function in chimeric combinations to control viral receptor and transport functions.
 ...
PMID:Control of cationic amino acid transport and retroviral receptor functions in a membrane protein family. 819 86

A decrease in protein kinase C activity caused either by treatment with inhibitors, such as staurosporine or H-7, or by prolonged exposure to phorbol diesters has been proposed to be involved in the early events of SH-SY5Y neuroblastoma cell differentiation. Because eight distinct isoforms of protein kinase C with discrete subcellular and tissue distributions have been described, we determined which isoforms are present in SH-SY5Y cells and studied their modifications during differentiation. The alpha, beta 1, delta, and epsilon isoforms were present in SH-SY5Y cells, as well as in rat brain. Protein kinase C-alpha and -beta 1 were the most abundant isoforms in SH-SY5Y cells, and immunoreactive protein kinase C-delta and -epsilon were present in much smaller amounts than in rat brain. Subcellular fractionation and immunocytochemistry demonstrated that all four isoforms are distributed bimodally in the cytoplasm and the membranes. Immunocytochemical analysis showed that the alpha isoform is associated predominantly with the plasma membrane and the processes extended during treatment with 12-tetradecanoyl-13-acetyl-beta-phorbol or staurosporine, and that protein kinase C-epsilon is predominantly membrane-bound. Its localization did not change during differentiation. Western blots of total SH-SY5Y cell extracts and of subcellular fractions probed with isoform-specific polyclonal antibodies showed that when SH-SY5Y cells acquired a morphologically differentiated phenotype, protein kinase C-alpha and -epsilon decreased, and protein kinase C-beta 1 did not change. These data suggest distinct roles for the different protein kinase C isoforms during neuronal differentiation, as well as possible involvement of protein kinase alpha and epsilon in neuritogenesis.
 ...
PMID:Differential expression and subcellular localization of protein kinase C alpha, beta, gamma, delta, and epsilon isoforms in SH-SY5Y neuroblastoma cells: modifications during differentiation. 841 48

We studied the morphology of bipolar cells in fixed vertical tissue sections of the rat retina by injecting the cells with Lucifer Yellow and neurobiotin. In addition to the rod bipolar cell, nine different putative cone bipolar cell types were distinguished according to the position of their somata in the inner nuclear layer and the branching pattern and stratification level of their axon terminals in the inner plexiform layer. Some of these bipolar cell populations were labeled immunocytochemically in vertical and horizontal sections using antibodies against the calcium-binding protein recoverin, the glutamate transporter GLT-1, the alpha isoform of the protein kinase C, and the Purkinje cell marker L7. These immunocytochemically labeled cell types were characterized in terms of cell density and distribution. We found that rod bipolar cells and GLT-1-positive cone bipolar cells occur at higher densities in a small region located in the upper central retina. This area probably corresponds to the central area, which is the region of highest ganglion cell density. A second peak of rod bipolar cell density in the lower temporal periphery matches the retinal area of binocular overlap. The population densities of the immunocytochemically characterized bipolar cells indicate that at least 50% of all bipolar cells are cone bipolar cells. The variety and total number of cone bipolar cells is surprising because the retina of the rat contains 99% rods. Our findings suggest that cone bipolar cells may play a more important role in the visual system of the rat than previously thought.
 ...
PMID:Immunocytochemical identification of cone bipolar cells in the rat retina. 855 Aug 93

Certain protein kinase C (PKC) isotypes are localized to the nucleus during cellular proliferation in murine erythroid cells, as well as in human promyelocytic leukemia and erythroleukemia cells. Because the structure of these PKC isotypes contains a conserved cysteine-rich region that contains the zinc finger DNA binding motif, we tested the hypothesis that selected PKC isotypes found in Friend erythroleukemia cells can bind to DNA. Cell lysates from murine Friend erythroleukemia cells, which express alpha, beta I, and beta II PKC, expressed greater amounts of the beta isoforms than the alpha isoform of PKC in their nuclei, and PKC beta I was found in the chromatin of these cells. Lysates of these cells were tested for their ability to bind to a DNA-cellulose column. Bound proteins were eluted with a step gradient of increasing KCl concentrations, and eluant fractions were then subjected to immunoblot analysis using isotype-specific antibodies to the alpha and beta I isotypes of PKC. DNA binding was detected for the PKC beta I isotype, which is present in the nucleus, but not for the more abundant PKC alpha isotype, which resides primarily in the cytoplasm. These results demonstrate that PKC can associate with DNA, and that this association is isotype specific in Friend erythroleukemia cells.
 ...
PMID:Protein kinase C beta from Friend erythroleukemia cells is associated with chromatin and DNA. 856 55

Among 11 isoforms of protein kinase C (PKC), we previously reported that the eta isoform of PKC plays a crucial role in mediating differentiation of keratinocytes. Activation of PKC is associated with its intracellular translocation from the cytoplasm to the plasma membrane, followed by down-regulation through proteolytic cleavage of the PKC molecules. In the present study, we demonstrated that the eta isoform of PKC is unique in that it is not translocated nor down-regulated upon stimulation. The level of the eta isoform, assayed by immunoblotting, remained unchanged during the first 12 h and then increased slightly up to 24 h when treated with tumor promoters or activators of PKC in constitutively expressing normal human keratinocytes. The activity of the eta isoform also remained unchanged after the 12-O-tetradecanoyl-phorbol-13-acetate treatment, as judged by binding ATP analog, autophosphorylation, and phosphorylation of an exogenous substrate. The alpha isoform of PKC, however, was rapidly down-regulated and was undetectable by 6 h after the treatment. These observations were further confirmed by immunohistochemical staining of normal human keratinocytes and transiently expressing COS1 cells. In addition, although the alpha isoform rapidly translocated to the plasma membrane, the eta isoform remained in the cytoplasm.
 ...
PMID:Absence of down-regulation and translocation of the eta isoform of protein kinase C in normal human keratinocytes. 861 24


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