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)

We are interested in whether lipocortins/annexins are involved in the response of human vascular endothelial cells (HUVEC) to angiogenic bFGF. Previously, a lipocortin/annexin of type I (p34) and a lipocortin/annexin of type VI were found to be associated with plasma membranes of HUVEC. Here we show that: i) phorbol ester PMA, a known activator of protein kinase C, possesses the property of acting synergistically with bFGF to stimulate DNA-primary initiation activity; ii) p69 is only detectable in membrane preparations from G1 phase HUVEC, whereas p34 is found to be present in membranes of G1 and S phase HUVEC; iii) the combination of bFGF and PMA induces an increased phosphorylation of p69 in late G1 phase. In contrast, phosphorylation of p34 occurs only in the S phase when HUVEC are treated with bFGF for an appreciable time lag (> or = 30 min) at 37 degrees C; iv)p69-enriched extracts from bFGF/PMA-treated HUVEC are found to be capable of enhancing the phospholipase A2 (PLA2)-catalyzed production of arachidonic acid in vitro; v) the DNA-synthetic response to bFGF plus PMA is consequent on stimulation of PLA2 and arachidonate production in late G1. These results suggest that p69 is directly connected to the mitogenic signal mechanism of bFGF in late G1, whereas p34 is associated with the endocytic process of this factor in S phase.
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PMID:[Response of human vascular endothelium to angiogenic fibroblast growth factor: role of 2 lipocortins/annexins]. 130 31

Phorbol-12,13-dibutyrate and 1,2-dioctanoylglycerol, activators of protein kinase C (PKC) that stimulate DNA synthesis in serum-deprived Swiss 3T3 fibroblasts, induce histone H1 kinase activity associated with anti-cdc2 immunoprecipitates after a lag period of 15h, a time point close to G1/S boundary of the cell cycle in these cells. Downregulation of PKC does not affect the basal cdc2 kinase activity, but potently inhibits both phorbol dibutyrate- and dioctanoylglycerol-induced cdc2 kinase activation. Phorbol dibutyrate induces a dramatic increase in the p34cdc2 protein level as well as the appearance of p35-p36 forms of cdc2 on Western blot. In PKC-downregulated cells, the p34 form of cdc2 remains elevated but p35-p36 forms do not appear upon phorbol dibutyrate stimulation. These results demonstrate that PKC activation leads to cdc2 kinase activation in mitogenically responsive Swiss 3T3 cells, and strongly suggest that both expression of p34cdc2 protein and its posttranslational modification(s) are involved in this process. Western blot analysis of PKC isozymes suggests that either PKC alpha, PKC delta or PKC epsilon may be involved in p34cdc2 kinase activation and mitogenesis.
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PMID:Activators of protein kinase C induce p34cdc2 histone H1 kinase stimulation in Swiss 3T3 fibroblasts. 144 45

The effect of ionizing radiation on the expression of two DNA-damage-inducible genes, designated gadd45 and gadd153, was examined in cultured human cells. These genes have previously been shown to be strongly and coordinately induced by UV radiation and alkylating agents in human and hamster cells. We found that the gadd45 but not the gadd153 gene is strongly induced by X rays in human cells. The level of gadd45 mRNA increased rapidly after X rays at doses as low as 2 Gy. After 20 Gy of X rays, gadd45 induction, as measured by increased amounts of mRNA, was similar to that produced by the most effective dose of the alkylating agent methyl methanesulfonate. No induction was seen after treatment of either human or hamster cells with 12-O-tetradecanoylphorbol-13-acetate, a known activator of protein kinase C (PKC). Therefore, gadd45 represents the only known mammalian X-ray-responsive gene whose induction is not mediated by PKC. However, induction was blocked by the protein kinase inhibitor H7, indicating that induction is mediated by some other kinase(s). Sequence analysis of human and hamster cDNA clones demonstrated that this gene has been highly conserved and encodes a novel 165-amino-acid polypeptide which is 96% identical in the two species. This gene was localized to the short arm of human chromosome 1 between p12 and p34. When induction in lymphoblast lines from four normal individuals was compared with that in lines from four patients with ataxia telangiectasia, induction by X rays of gadd45 mRNA was less in the cell lines from this cancer-prone radiosensitive disorder. Our results provide evidence for the existence of an X-ray stress response in human cells which is independent of PKC and which is abnormal in taxia telangiectasia.
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PMID:Induction by ionizing radiation of the gadd45 gene in cultured human cells: lack of mediation by protein kinase C. 199 Feb 62

We previously reported that topical application of 12-o-tetradecanoylphorbol-13-acetate to mouse skin causes phosphorylation of epidermal proteins with molecular weights of 40,000 (p40) and 34,000 (p34). In the accompanying paper, p40 was identified as creatine phosphokinase B. Here we report that both in intact cells and in a cell-free system, phosphorylation of creatine hosphokinase B by protein kinase C resulted in an increase in its ability to catalyze the transfer of the high-energy phosphate of phosphocreatine to ADP, thereby producing ATP. H-7, a specific inhibitor of protein kinase C was found to abolish the increase in enzyme activity. Lineweaver-Burk plot analysis indicated that the increased activity was mostly due to a decreased Km for phosphocreatine. Phosphorylation and activation of creatine phosphokinase B may be a physiological response to maintain ATP balance when a protein kinase C pathway is stimulated.
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PMID:Regulation of creatine phosphokinase B activity by protein kinase C. 225 25

We previously described epidermal proteins with molecular weights of 40,000 (p40) and 34,000 (p34) as target proteins of protein kinase C in mouse skin carcinogenesis in vivo. In the present work, p40 was purified from mouse brain by the use of 32P-labeled p40 of BALB/MK-2 cells as a tracer. Following four lines of evidence indicate that p40 is creatine phosphokinase B. 1) The amino acid sequences of all peptide fragments of p40 from mouse brain were located in the primary structure of creatine phosphokinase B. 2) p40 of BALB/MK-2 cells was immunoprecipitated with goat antibody against human creatine phosphokinase B. 3) p40 of BALB/MK-2 cells was absorbed to and eluted from a creatine affinity column. 4) Purified creatine phosphokinase B was phosphorylated in vitro by purified protein kinase C, but not by cAMP-dependent kinase or casein kinase II.
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PMID:Purification and identification of creatine phosphokinase B as a substrate of protein kinase C in mouse skin in vivo. 225 26

A 1.4 kb region downstream of the DNA polymerase gene of Autographa californica nuclear polyhedrosis virus was sequenced. Two open reading frames (ORFs) were identified of 927 and 474 bases in length. The 927 base ORF encodes a 34.8K protein as determined by in vitro translation of both hybrid-selected RNA and RNA synthesized in vitro from a 927 base ORF template. The predicted amino acid sequence of the 34.8K polypeptide (p34.8) reveals a hydrophobic N terminus, two potential N-glycosylation sites, and potential sites for phosphorylation by casein kinase I and protein kinase C. The p34.8 gene has a strong codon usage bias which is strikingly different from that of the polyhedrin gene. The two 5' ends of the 927 base ORF transcripts initiate from an ATAAG sequence and a GTAAG sequence 11 and 87 bases upstream of the ATG codon respectively. A short upstream reading frame is present in the leader sequence of the longer RNA. The transcripts have multiple 3' ends; the most proximal endpoint correlates with a polyadenylation signal overlapping the translational termination codon of the 927 base ORF. Transcripts of the latter were not observed early in the infection cycle but appeared 6 h after infection and were maximally expressed at 12 to 24 h post-infection. The late nature of these transcripts was confirmed by their sensitivity to aphidicolin and cycloheximide, inhibitors of DNA replication and protein synthesis respectively. Attempts to construct viral mutants carrying a deletion of the p34.8 gene and fusion with the beta-galactosidase gene suggest that the former gene is essential for viral replication.
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PMID:Sequence, transcription and translation of a late gene of the Autographa californica nuclear polyhedrosis virus encoding a 34.8K polypeptide. 267 27

Activation of protein kinase C (PKC) and the resulting phosphorylations of proteins in vivo were examined in mouse epidermis, a target tissue of tumor-promoting phorbol diesters, such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Treatment of mouse skin with TPA caused rapid translocation of PKC from the cytosol to the membrane fraction of skin tissue, followed by its down regulation. Epidermal proteins were labeled locally with 32P using the ring-shaped forceps technique that economizes on the amount of 32Pi required. Treatment with TPA in vivo resulted in about 2-fold increases in the phosphorylations of epidermal proteins with molecular weights of 34,000 and 40,000 and isoelectric points of 4.7-5.1 and 5.2-6.2 (p34 and p40, respectively). The phosphorylations of these proteins were also stimulated by teleocidin B. Inhibitors of PKC, such as chlorpromazine, quercetin, and staurosporine inhibited these increases in phosphorylations of p34 and p40 on TPA treatment. Furthermore, p34 and p40 were phosphorylated by purified PKC in a cell-free system. These results indicate that p34 and p40 are phosphorylated by PKC in mouse epidermis in vivo and may be involved in tumor promotion.
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PMID:Phosphorylations of Mr 34,000 and 40,000 proteins by protein kinase C in mouse epidermis in vivo. 313 9

The effects of protein kinase C inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine) on tumor-promoting phorbol ester induced inhibition of vincristine uptake in P388 murine leukemic cells were investigated with the objective of assessing the possible role of Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C) in vincristine uptake. 12-O-Tetradecanoylphorbol-13-acetate (TPA) is a potent inhibitor at concentrations above 1 nM. Other phorbol esters also inhibited vincristine uptake in approximate proportion to their activity in competing for [20-3H]phorbol 12,13-dibutrate binding. TPA enhanced the Ca2+-activated, phospholipid-dependent phosphorylation of histone III-S by a soluble protein fraction of cells. Phosphorylation of various cell lysate proteins (p18, p21, p29, p34 and p45) were also stimulated by TPA. These TPA-induced stimulations were also inhibited dose-dependently by H-7. It is tentatively concluded that the phosphorylation of cell lysate protein substrates by protein kinase C may be an important mechanism linked to the regulation of vincristine uptake in leukemic cell.
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PMID:An inhibitor of protein kinase C, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine(H-7) inhibits TPA-induced reduction of vincristine uptake from P388 murine leukemic cell. 376 16

Entry into mitosis requires the coordinated action of multiple mitotic protein kinases. In this report, we investigate the involvement of protein kinase C in the control of mitosis in human cells. Treatment of synchronized HL60 cells with the highly selective protein kinase C (PKC) inhibitor chelerythrine chloride leads to profound cell cycle arrest in G2 phase. The cellular effects of chelerythrine are not due to either direct or indirect inhibition of the known mitotic regulator p34(cdc2)/cyclin B kinase. Rather, several lines of evidence demonstrate that chelerythrine-mediated G2 phase arrest results from selective inhibition and degradation of betaII protein kinase C. First, chelerythrine causes dose-dependent inhibition of betaII PKC in vitro with an IC50 identical to that for G2 phase blockade in whole cells. Second, chelerythrine specifically inhibits betaII PKC-mediated lamin B phosphorylation and mitotic nuclear lamina disassembly. Third, chelerythrine leads to selective loss of betaII PKC during G2 phase in synchronized cells. Fourth, chelerythrine mediates activation-dependent degradation of PKC, indicating that betaII PKC is selectively activated during G2 phase of cell cycle. Taken together, these data demonstrate that betaII PKC activation at G2 phase is required for mitotic nuclear lamina disassembly and entry into mitosis and that betaII PKC-mediated phosphorylation of nuclear lamin B is important in these events.
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PMID:betaII protein kinase C is required for the G2/M phase transition of cell cycle. 866 71

Disassembly of the sperm nuclear envelope at fertilization is one of the earliest events in the development of the male pronucleus. We report that nuclear lamina disassembly in interphase sea urchin egg cytosol is a result of lamin B phosphorylation mediated by protein kinase C (PKC). Lamin B of permeabilized sea urchin sperm nuclei incubated in fertilized egg G1 phase cytosolic extract is phosphorylated within 1 min of incubation and solubilized prior to sperm chromatin decondensation. Phosphorylation is Ca2+-dependent. It is reversibly inhibited by the PKC-specific inhibitor chelerythrine, a PKC pseudosubstrate inhibitor peptide, and a PKC substrate peptide, but not by inhibitors of PKA, p34(cdc2) or calmodulin kinase II. Phosphorylation is inhibited by immunodepletion of cytosolic PKC and restored by addition of purified rat brain PKC. Sperm lamin B is a substrate for rat brain PKC in vitro, resulting in lamin B solubilization. Two-dimensional phosphopeptide maps of lamin B phosphorylated by the cytosolic kinase and by purified rat PKC are virtually identical. These data suggest that PKC is the major kinase required for interphase disassembly of the sperm lamina.
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PMID:Protein kinase C-mediated interphase lamin B phosphorylation and solubilization. 926 Nov 38


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