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)

We examined the levels of protein kinase C (PKC) activity and the expressions of its three major isozymes, designated types I (gamma), II (beta), and III (alpha), in the cytosol and particulate fractions of cells from patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL), in an attempt to elucidate the cell type- or lineage-specific expression of these isozymes. The levels of PKC activities in the cytosol and particulate fractions from AML cells were higher than those from ALL or CLL cells. The average PKC activities of AML cells, ALL cells, and CLL cells were 18.7, 12.2, and 11.3 pmol/min/10(8) cells, respectively, in the cytosol fractions and 4.4, 3.1, and 2.6 pmol/min/10(8) cells, respectively, in their particulate fractions. M1 cells (French-American-British classification) and AML cells with T-lymphocyte-associated surface antigens, such as CD2 and CD7, had significantly lower PKC activities among AML cells. Immunoblot analyses using monoclonal antibodies against each isozyme revealed that all three isozymes were broadly distributed on leukemic cells with considerable variability in the level of expression. All lymphoid leukemic cells expressed PKC-gamma in the cytosol fractions, albeit a minor component; however, this type was observed in cells from only half the number of AML patients. Those AML cells with cytosolic PKC-gamma usually expressed lymphoid surface antigens, such as CD2, CD7, and CD19. On the other hand, cytosolic PKC-beta and PKC-alpha were commonly observed in all types of leukemic cells. AML cells expressed these two types at almost equal levels, but in lymphoid cells, expressions of PKC-beta were usually more abundant than those of PKC-alpha. These data suggest that AML cells with lymphoid antigens might have a lower PKC activity but more predominant expression of cytosolic PKC-gamma than the usual AML cells.
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PMID:Expression of three major protein kinase C isozymes in various types of human leukemic cells. 186 47

The appearance of the biphasic insulin secretory response several days after birth suggests that maturation of a critical step in stimulus-secretion coupling occurs during the early neonatal period. To clarify the role of protein kinase C (PKC) during this time, we examined the pancreatic islets of adult, 3-day neonatal, and 19-day fetal rats for the presence of different PKC isoenzymes. Western-blot analysis of islet extracts showed the presence of PKC isoforms in both adult and neonatal tissues. Immunocytochemistry of adult islets revealed a differential expression in islet cell types. PKC-alpha was found only in beta-cells, PKC-gamma in alpha-cells, and PKC-epsilon in delta-cells and vascular walls. Immunoreactivity for PKC-beta was not detected in any cell type. All three isoenzymes were also present in neonatal islets; however, in contrast to adult tissue, immunoreactivity for either PKC-alpha or PKC-gamma was present in relatively few cells. There was no apparent immunoreactivity for PKC-alpha or PKC-gamma in fetal islets, although these tissues contained strong staining for insulin and glucagon. These data show that three of the PKC isoforms are restricted to a particular islet cell type, where they may play a unique role in the secretion of a specific hormone. Moreover, our results demonstrate that these enzymes, especially PKC-alpha, appear during the early neonatal period. This age-dependent expression may be linked to the development of the biphasic insulin release response.
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PMID:Age-dependent expression of protein kinase C isoforms in rat islets. 193 8

We have studied the expression of mRNA encoding all known protein kinase C (PKC) isozymes (alpha, beta, gamma, delta, epsilon, zeta, and eta) in murine tumor cell lines that exemplify hemopoietic cells arrested at different stages of development as well as in normal hemopoietic cells. We demonstrate that some of the isozymes, PKC-alpha, -beta, and -eta, are differentially expressed in different lineages. PKC-alpha and -beta generally are not detectable in myeloid cell lines, where PKC-delta is the predominant isoform. Both PKC-alpha and -beta are abundant in most T and B lymphocytic lines, but steady state levels of PKC-beta mRNA are lowest in plasma cell tumors, which exemplify the terminally differentiated B lymphocyte. In contrast, the levels of PKC-alpha mRNA remain high in plasma cell tumors, and a novel, 2.5-kb PKC-alpha mRNA gains prominence. PKC-eta mRNA is the major PKC isoform expressed in T lymphocytes, but it also is highly abundant in some myeloid lines. PKC-delta is expressed at high levels in all the lines we studied, whereas PKC-epsilon and -zeta are found in most cells but only at rather low levels. Analysis of myeloid clones derived from bipotential B lineage progenitor cell lines suggests that the B cell phenotype is associated with the expression of PKC-alpha. The close correlation of protein levels with mRNA levels indicates that PKC expression in hemopoietic cells is mainly regulated at the level of mRNA. The lineage- and differentiation stage-specific patterns of PKC-isozyme expression presented here suggest the involvement of specific PKC isozymes in differentiation as well as lineage determination of hemopoietic cells.
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PMID:Expression of protein kinase C genes in hemopoietic cells is cell-type- and B cell-differentiation stage specific. 194 Mar 80

Glomerular mesangial cells have been shown to express two protein kinase C (PKC) isozymes, PKC-alpha and PKC-epsilon. Upon long-term treatment with phorbol ester PKC-alpha is depleted faster than PKC-epsilon. Here we demonstrate that removal of phorbol ester results in a differential recovery of PKC-alpha and -epsilon isozymes. Whereas PKC-epsilon starts to recover within 1h, PKC-alpha does not begin to recover before 4 h after removal of phorbol ester. These data suggest a differential rate of protein synthesis of PKC-alpha and -epsilon. In parallel to the recovery of PKC isozymes mesangial cells also regained their functional responsiveness, i.e., stimulation of prostaglandin synthesis and feedback inhibition of angiotensin II-stimulated InsP3 formation.
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PMID:Differential recovery of protein kinase C-alpha and -epsilon isozymes after long-term phorbol ester treatment in rat renal mesangial cells. 195 88

It is known that PKC is differently expressed in brain and the peripheral nervous system and is involved in cellular differentiation. We have analyzed 9 human neuronal-derived crest-cell lines for PKC-alpha mRNA. Seven out of nine expressed 9.0 kb and 4.0 kb PKC-alpha mRNAs, but three had high level of 9.0 kb transcription. The different expression of the two messenger RNAs may result from alternative splicing and a different degree of cell maturation. The same cell lines were studied for MYCN gene expression. A possible relation between the two genes is discussed. One cell line expressing high levels of both PKC-alpha mRNA was treated with 10(-5) M retinoic acid (RA). The expression of both messenger RNAs was suppressed when the cells achieved a morphological differentiation and showed neurite-like processes. A decrease of PKC-alpha gene expression was associated to down regulation of MYCN mRNA. These preliminary results suggest that PKC suppression of PKC-alpha mRNA is associated with reversion of the malignant phenotype.
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PMID:Expression of protein kinase C-alpha (PKC-alpha) and MYCN mRNAs in human neuroblastoma cells and modulation during morphological differentiation induced by retinoic acid. 201 16

The expression of the different protein kinase C (PKC) isozymes in mouse thymocytes was studied to determine if there is a correlation between isozyme expression and thymocyte phenotype. Expression of PKC isozymes in thymocyte subsets (distinguished by the CD4 or CD8 Ag) was determined by message amplification phenotyping. The expression of mRNA for PKC-alpha, -beta, -epsilon, and -zeta, but not -gamma or -delta isozymes, was detected in all of the unstimulated thymocyte subpopulations analyzed. Thus no differences in the pattern of PKC isozyme expression were found that could be correlated with thymocyte phenotype. However, it was noted that the levels of PKC mRNA expression were affected by different stimuli in unfractionated thymocytes. Whereas mRNA levels of PKC-alpha and -beta were down-regulated by PMA and ionomycin treatment, no significant changes were seen in the levels of PKC-epsilon mRNA with these agents. PKC-epsilon mRNA decreased in thymocytes exposed to Con A similar to what has been reported for PKC-epsilon protein. PKC-zeta mRNA was also down-regulated by PMA or ionomycin, and the combination of both compounds caused a more rapid and drastic effect. Finally, PKC-delta mRNA expression was induced transiently in thymocytes only after exposure to PMA or Con A, and this induction was inhibited by ionomycin treatment. These results indicate that message levels of specific isoforms of PKC are uniquely regulated and suggest an additional level of control of PKC activity in activated lymphocytes.
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PMID:Expression of protein kinase C isoenzymes in thymocyte subpopulations and their differential regulation. 207 91

Of the recently described members of the protein kinase C (PKC) family (-delta, -epsilon, -zeta), no detailed properties of the purified enzymes have been presented. Here we describe the expression of PKC-epsilon in insect cells using a baculovirus vector. The recombinant enzyme has been purified to homogeneity by sequential chromatography on DEAE-cellulose, serine-Sepharose, Mono Q, and Superose 12; the protein shows a molecular mass of 90 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. PKC-epsilon is dependent upon phospholipid and diacylglycerol (or phorbol esters) for activity and displays a pattern of specificity for these effectors similar to other PKC isotypes. Similarly, inhibition of PKC-epsilon by staurosporine and H-7 parallels inhibition of other PKC isotypes. However, unlike PKC-alpha, -beta, and -gamma, PKC-epsilon shows no dependence upon Ca2+. Furthermore, the substrate specificity of PKC-epsilon is quite different from other characterized PKCs. The importance of functional diversity within the PKC family is discussed.
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PMID:Expression, purification, and characterization of protein kinase C-epsilon. 218 43

In this study we examined the effects of insulin on protein kinase C (PKC) activity in cultured fetal chick neurons. PKC activity, measured as 32P incorporation into histone H1 in the presence of calcium (500 microM), phosphatidylserine (100 micrograms/ml), and diolein (3.3 micrograms/ml) minus the incorporation in the presence of calcium alone, was detected in neuronal cytosolic (207 +/- 33 pmol/min/mg) and membrane (33 +/- 8 pmol/min/mg) fractions. Insulin added to intact neurons increased the activity of PKC in both cytosolic and membrane fractions by about 40%. Neurons preincubated with cycloheximide (10 micrograms/ml) 30 min prior to insulin treatment showed the same degree of stimulation of PKC activity by insulin. The activation of PKC was maximal within 5-10 min of insulin exposure and was sustained for at least 60 min. Insulin stimulated PKC in a dose-dependent manner, with a maximal response obtained at 100 ng/ml. Addition of phosphatidylserine and diolein to neuronal cell extracts resulted in the phosphorylation of four major cytosolic proteins (70, 57, 18, and 16 kDa) and one major membrane protein (75 kDa). Phosphorylation of all five proteins was increased 2-fold in extracts from insulin-treated neurons. Immunoblot analysis of whole cell extracts using antibodies against PKC-alpha, PKC-beta, PKC-gamma, PKC-delta, and PKC-epsilon revealed that cultured fetal chick neurons contained only one of these PKC isoforms, the epsilon-isoform. The enzyme was mostly cytosolic. Insulin had no effect on either the amount of distribution of PKC-epsilon in cultured neurons but induced a small change in the mobility of PKC-epsilon on sodium dodecyl sulfate-polyacrylamide gels. When assay conditions were designed to measure specifically the activity of PKC-epsilon, using a synthetic peptide substrate in the absence of calcium, activity was 50 +/- 12% higher in insulin-treated cells (p less than 0.005). PKC activity in control and insulin treated-neurons was almost completely inhibited when assays included a peptide identical to the pseudo-substrate binding site of PKC-epsilon. We conclude that PKC-epsilon is the major PKC isoform present in cultured fetal chick neurons. Insulin stimulates PKC-epsilon activity by a mechanism that does not involve translocation of the enzyme from cytosol to membrane.
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PMID:Insulin stimulates the activity of a novel protein kinase C, PKC-epsilon, in cultured fetal chick neurons. 220 68

The isoform pattern of protein kinase C (PKC) was examined in wild-type and Adriamycin-resistant (HL-60/AR) HL-60 leukemia cells. Analyses were carried out by immunoblotting with mouse monoclonal antibodies against PKC-alpha and PKC-beta and a rabbit polyclonal antibody against the variable (V3) region of PKC-gamma. HL-60/AR cells contained an equivalent level of PKC-alpha and a lower amount of PKC-beta than HL-60 cells. In contrast, only HL-60/AR cells contained PKC-gamma. These results indicate that the regulation of this family of isoenzymes is altered in drug-resistant cells.
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PMID:Protein kinase C-gamma is present in adriamycin resistant HL-60 leukemia cells. 230 37

A protein kinase C alpha (PKC alpha) cDNA confers increased phorbol ester binding activity to intact cells when transiently expressed in COS cells or expressed stably in transfected rat 3Y1 fibroblasts. A point mutant (PKC alpha K----R) of PKC alpha, where Lys368 at the putative ATP-binding site is replaced with Arg, confers enhanced phorbol ester binding activity to both transiently and stably expressed COS and 3Y1 cells, respectively. Like endogenous and exogenously expressed wild type PKC alpha, the mutant PKC alpha K----R is translocated from the cytosol to the particulate fraction when cells are treated with a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). On the other hand, the mutant PKC alpha K----R is not degraded when cells are treated with TPA, making a clear contrast to wild type PKC alpha; i.e. the mutant is resistant to TPA-mediated down-regulation. The mutant lacks kinase activity as expected, as judged by autophosphorylation and by a kinase assay using a peptide substrate, although the phorbol ester binding activity remains intact. These results suggest a link between the kinase activity of PKC alpha and the sensitivity to TPA-mediated proteolytic degradation. We propose that autophosphorylation of PKC alpha is a prerequisite for proteolytic cleavage associated with the down-regulation of PKC alpha.
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PMID:A point mutation at the putative ATP-binding site of protein kinase C alpha abolishes the kinase activity and renders it down-regulation-insensitive. A molecular link between autophosphorylation and down-regulation. 231 54


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