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)

The reason for different phosphorylation of topoisomerase I in two sublines of L5178Y murine lymphoma (LY cells) was investigated. Camptothecin-resistant LY-S cells show increased poly(ADP-ribose) level and lowered topoisomerase I phosphorylation compared to camptothecin-sensitive LY-R cells. In this study diminished phosphorylation of LY-S topoisomerase I was observed for sites recognized by casein kinase 2 but not for those phosphorylated by protein kinase C. Tryptic digests of LY-S topoisomerase I labeled in vitro by casein kinase 2 indicated that phosphorylation was similarly lowered at different sites. Activity of casein kinase 2 measured in nuclear extracts was about 1.7 times lower for LY-S than LY-R cells. This difference was diminished or eliminated by increasing casein concentration, diluting the extract or increasing the ionic strength. Activity of poly(ADP-ribose) polymerase was 5.3 times higher in LY-S than in LY-R nuclei. When the activity of the polymerase was inhibited by treatment of LY-S cells with benzamide, casein kinase 2-catalyzed phosphorylation of topoisomerase I increased. This was accompanied by an increase in sensitivity to camptothecin as reflected in the diminished viability of LY-S cells.
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PMID:Phosphorylation of topoisomerase I in L5178Y-S cells is associated with poly(ADP-ribose) metabolism. 863 Nov 20

Sets of peptides with defined sequences, each on a separate spot, were synthesized simultaneously on continuous cellulose membranes (SPOTs membranes), which were originally designed for epitope studies. The applicability of the membrane-bound peptides as substrates for protein kinases was tested using protein kinase A, protein kinase C and casein kinases I and II as model enzymes. We found that the peptide-membrane complexes can serve as kinase substrates. Our results suggest that membrane-bound peptides offer a new potential for the investigation of substrate specificity of protein kinases. An advantage to this method is that there is no need for substrate identification and separation, which is required with high-volume random peptide libraries. Membrane-bound peptides may even form a basis for kinase assays with peptides lacking multiple basic amino acids, required for separation of the substrates in conventional assays. Problems connected with protein kinase substrate specificity can be investigated in any laboratory using the rapid and inexpensive SPOTs technique, as neither costly apparatus nor special experience in peptide synthesis is necessary.
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PMID:Simultaneously synthesized peptides on continuous cellulose membranes as substrates for protein kinases. 872 78

Curcumin [diferuloylmethane; 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione], a major bioactive secondary metabolite found in the rhizomes of turmeric (Curcuma longa), is an inhibitor of Ca(2+)- and phospholipid-dependent protein kinase C (PKC) and of the catalytic subunit (cAK) of cyclic AMP-dependent protein kinase (IC50 values 15 and 4.8 microM, respectively). Curcumin inhibits plant Ca(2+)-dependent protein kinase (CDPK) (IC50 41 microM), but does not inhibit myosin light chain kinase or a high affinity 3',5'-cyclic AMP-binding phosphatase. Curcumin inhibits cAK, PKC and CDPK in a fashion that is competitive with respect to both ATP and the synthetic peptide substrate employed. The IC50 values for inhibition of cAK by curcumin are very similar when measured with kemptide (LRRASLG) (in the presence or absence of ovalbumin) or with casein or histone III-S as substrates. However, the presence of bovine serum albumin (0.8 mg ml-1) largely overcomes inhibition of cAK by curcumin.
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PMID:Inhibition of cyclic AMP-dependent protein kinase by curcumin. 876 15

Ingestion of protein deficient diet is known to decrease the enzyme load, particularly drug metabolising enzymes in liver. It also leads to decrease in polyphosphoinositide pool in brain and kidney. Therefore, changes in protein kinase C activity and its translocation were speculated and studied in brain, lung, heart, spleen, liver and kidney of rats maintained on three different diets, viz. casein (20% protein) deficient (4% protein, rice flour as protein source) and supplemented (deficient diet supplemented with L-lysine and DL-threonine), for 28 days. A significant alteration in total protein kinase C activity and/or its translocation was observed in these tissues in the deficient group in comparison to casein group. Supplementation of diet with L-lysine and DL-threonine could partially reverse the affect. These changes in protein kinase C activity and its translocation indicate alteration in the mechanism of signalling system in dietary protein deficiency and hence an altered response of tissues to the external stimuli in dietary protein deficiency.
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PMID:Effect of dietary protein manipulation on translocation of protein kinase C activity in various tissues of rats. 878 Oct 28

A M(r) 25,000 protein, which was isolated from the cytosolic fraction of Xenopus laevis oocytes, is a newly identified substrate for casein kinase II and protein kinase C [Hashimoto et al. (1995) J. Biochem. 118, 453-460], and was recently shown to have the ability to modulate protein phosphatase 2A activity [Hashimoto et al. (1996) J. Biochem. 119, 626-632]. Acid phosphatase treatment of the protein shifted its electrophoretic mobility from 25 to 20 kDa on SDS-PAGE. The content of alkali-labile phosphate bound covalently to the protein was 53 mol per mol of M(r) 25,000 protein. Amino acid composition analysis revealed that there are 50 serine residues and 6 threonine residues per mol of this protein. Therefore, this M(r) 25,000 protein seems to be highly phosphorylated in vivo. The M(r) 25,000 protein, once partially dephosphorylated by acid phosphatase, served as an efficient substrate for casein kinase I and casein kinase II. When entirely dephosphorylated, the M(r) 25,000 protein was used as a substrate, the rate of phosphorylation with both casein kinases being decreased. This behavior of casein kinases toward the M(r) 25,000 protein reflects the possible mechanism of multisite phosphorylation in which the introduction of a phosphate group facilitates sequential phosphorylation.
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PMID:Studies on the phosphorylation of a M(r) 25,000 protein, a putative protein phosphatase 2A modulator, by casein kinase I, and analysis of multiple endogenous phosphates. 879 4

The purpose of the present study was to investigate, in force-fed rats, whether alimentary zinc (Zn) deficiency affects the activity of the Zn-metalloenzyme protein kinase C (PKC). The in vivo activity of PKC was determined by measuring the subcellular distribution of the enzyme between the cytosolic and the particulate fraction in brain and muscle. For this purpose, 24 male Sprague-Dawley rats with an average live mass of 126 g were divided into 2 groups of 12 animals each. The Zn-deficient and the control rats received a semisynthetic casein diet with a Zn content of 1.2 and 24.1 ppm, respectively. All animals were fed four times daily by gastric tube in order to ensure that the depleted animals also received adequate nutrients and to synchronize the feed intake exactly. After 12 d, the depleted rats were in a state of severe Zn deficiency, as demonstrated by a 70% lower serum Zn concentration and a 66% reduction in the serum activity of alkaline phosphatase. Neither the cytosolic nor the particulate fraction of the thigh muscle showed any difference between the depleted and the control animals as regards PKC activity/g of muscle. The specific activity of PKC/mg of protein in the cytosolic fraction of the muscle was not affected by alimentary zinc deficiency, whereas the specific activity of PKC in the particulate fraction of the muscle was reduced by a significant 10% in Zn deficiency (150 +/- 12 vs 135 +/- 14 pmol P/min/mg protein). In the brain, neither the cytosolic nor the particulate fraction revealed any difference in PKC activity/g of fresh weight or in the specific activity/mg of protein between the control and the Zn-deficient rats.
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PMID:Activity and subcellular distribution of protein kinase C (PKC) in muscle and brain of force-fed zinc-deficient rats. 881 Dec 84

Using a DNA fragment derived from the Saccharomyces cerevisiae protein kinase C gene (PKC1) as a probe to screen an ordered array library of genomic DNA from the dimorphic pathogenic fungus Candida albicans, the C. albicans PKC1 gene (CaPKC1) was isolated. The CaPKC1 gene is predicted to encode a protein of 1079 amino acids with 51% sequence identity over the entire length with the S. cerevisiae Pkc1 protein and is capable of functionally complementing the growth defects of a S. cerevisiae pkc1 delta mutant strain on hypo-osmotic medium. Deletion of both endogenous copies of the CaPKC1 gene in diploid C. albicans cells resulted in an osmotically remedial cell lysis defect of both the budding and the hyphal growth form and morphologically aberrant cells of the budding form. Despite these abnormalities, the transition between the two growth forms of C. albicans occurred normally in pkc1/pkc1 double disruptants. Capkc1p was modified at its C-terminus with two repeats of the Staphylococcus aureus protein A IgG-binding fragment (ZZ-sequence tag) and partially purified by chromatography on DEAE-Sepharose and IgG-Sepharose. In vitro, Capkc1p preferably phosphorylated the S. cerevisiae Pkc1p pseudosubstrate peptide and myelin basic protein, but not histones, protamine or dephosphorylated casein, and failed to respond to cofactors known to activate several mammalian PKC isozymes.
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PMID:The Candida albicans PKC1 gene encodes a protein kinase C homolog necessary for cellular integrity but not dimorphism. 881 61

Matrix metalloproteinases (MMPs) are a group of enzymes with the potential to degrade extracellular matrix proteins. One of the MMPs, stromelysin-1 (MMP-3) has been localized to extracellular matrix vesicles in growth plate chondrocyte cultures, suggesting involvement of this enzyme in remodeling of the extracellular matrix during endochondral development, a process which is regulated by the vitamin D metabolites, 1,25-(OH)2D3 and 24,25-(OH)2D3. To determine whether stromelysin-1 is regulated by vitamin D as well, confluent cultures of cells derived from growth zone (GC) and resting zone (RC) rat costochondral cartilage were treated with 1 alpha, 25-(OH)2D3 (1,25) and 24R,25-(OH)2D3 (24,25), respectively, and the effect on stromelysin-1 assessed by casein gel zymography and Western blots. Although stromelysin-1 activity was enriched in the matrix vesicle fraction, only the plasma membrane enzyme was affected by the treatment; 1, 25 and 24,25 caused a marked decrease in plasma membrane stromelysin-1 activity in their target cells. Since plasma membrane protein kinase C (PKC) activity is stimulated by 1,25 and 24,25, we hypothesized that stromelysin-1 activity was regulated by the vitamin D metabolites via PKC-dependent phosphorylation. To test this, membrane fractions (containing endogenous PKC alpha and zeta as well as stromelysin-1) were incubated in the presence of purified rat brain PKC and/or recombinant human (rh) stromelysin-1 and [gamma 32 P]-ATP and anti-stromelysin-1 immunoprecipitates were analyzed by autoradiography and Western blots. Immuno-phospho-stromelysin-1 was localized to a 52-kDa band in the plasma membrane fraction only; no phosphorylation was observed in the matrix vesicle fraction. Selective inhibitors of PKC activity demonstrated that phosphorylation was inhibited by H7 and low concentrations of H8, but not by HA1004, indicating that PKC, not PKA, was responsible. Protein phosphatase 2A1 (PP2A), a serine/threonine-specific phosphatase, selectively removed the radiolabel in a time-dependent manner, providing further support for a PKC-dependent phosphorylation mechanism. Incubation of resting zone cell plasma membranes with 24,25 but not 1, 25, resulted in phosphorylation of stromelysin-1, demonstrating that the nongenomic effect was metabolite-specific. This suggests that this may be one mechanism by which vitamin D metabolites regulate stromelysin-1 activity and that PKC-dependent phosphorylation inhibits the metalloproteinase.
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PMID:Vitamin D3 regulation of stromelysin-1 (MMP-3) in chondrocyte cultures is mediated by protein kinase C. 881 11

Oocytes from the Japanese clam Ruditapes philippinarum are naturally blocked at the prophase-I stage of meiosis. Following physiological activation by the neurohormone serotonin (5HT), oocytes undergo germinal vesicle breakdown (GVBD) and reach a second cell cycle arrest in metaphase-I. To identify the kinases activated during meiosis reinitiation, we used a phosphorylation assay following sodium dodecyl sulphate-polyacrylamide gel electrophoresis and in situ renaturation. A soluble 85-kDa serine/threonine kinase (PK85) was highly and consistently activated (up to 17-fold) within 5 minutes following addition of the hormone. This activation occurred 5 to 10 minutes before GVBD and only when 5HT concentration was sufficient to induce meiosis reinitiation. The calcium ionophore A23187 and NH4Cl, two compounds known to induce GVBD by increasing intracellular calcium concentration, also activate PK85. In crude oocyte extracts, the presence of beta-glycerophosphate, NaF, okadaic acid, calyculin A or microcystin, prevented inactivation of PK85, suggesting that it is activated by phosphorylation. Partial purification of PK85 followed by Western blotting showed that this kinase is related to the ribosomal S6 kinase pp90rsk. PK85 phosphorylates the peptides LRRASLG (kemptide) and PLARTLSVAGLPGGK (syntide-2), and to a lesser extent the synthetic polyamino acids poly(R3:S1) while myelin basic protein (MBP), histone III-S, casein, the peptides pEKRPSQRSKYL ((pGlu4)-MBP 4-14), GTFRASIRRLAARRR (NIMA kinase substrate), the protein kinase C (PKC) substrate LRTLRR and the synthetic polyaminoacids poly(R1:P1:T1) were poor substrates. 5HT-induced GVBD and PK85 activation are both inhibited by the phorbol ester 12-myristate 13-acetate (PMA) and this inhibition can be reversed by 5 microM of the bisindolyl-maleimide GF109203X, a potent PKC inhibitor. PMA inhibitory action appears to take place between 5HT binding to its receptor and the intracellular calcium surge since it has no effect on GVBD induced by calcium ionophore A23187 and thapsigargin. Taken together, these results suggest that serotonin-induced activation of PK85 occurs after the intracellular calcium surge in a PKC-independent pathway.
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PMID:Activation of an 85 kDa ribosomal S6 kinase during serotonin-induced oocyte maturation. 884 Jan 88

The purpose of the present study was to investigate whether alimentary zinc (Zn) deficiency affects the activities of the Zn metalloenzymes protein kinase C (pKC) and the phosphatidylinositol-specific phospholipase C (PLC) in force-fed Zn-deficient rats. The in vivo activity of pKC was determined by measuring the subcellular distribution of the enzyme between the cytosolic and the particulate fraction of erythrocytes, whereas the activity of PLC was measured indirectly through the concentration of its metabolite inositol-1,4, 5-trisphosphate (IP3) in platelets and monocytes. For this purpose, 24 male Sprague-Dawley rats with an average live mass of 126 g were divided into 2 groups of 12 animals each. The Zn-deficient and the control rats received a semisynthetic casein diet with a Zn content of 1.2 and 24.1 ppm, respectively. All animals were fed the same amount of the diet (10.8 g dry matter [DM]/d and rat) four times daily by gastric tube. After 12 d, the depleted rats were in a state of severe Zn deficiency, as demonstrated by a 70% lower Zn concentration and a 66% reduction in the serum activity of alkaline phosphatase. The radio-immunologically determined concentration of IP3 was reduced by a significant 55% in the platelets of the Zn-deficient rats (8.4 pmol IP3/ 5 x 10(8)) as compared with the control rats (18.8 pmol IP3/5 x 10(8)), whereas the IP3 concentration in the monocytes was not affected by the alimentary Zn supply (1.4 vs 1.2 pmol IP3/10(6)), nor was there any difference between the Zn-deficient and the control rats with regard to the radioenzymatically determined specific activity of pKC, either in the cytosolic fraction (32.7 vs 32.5 pmol P/min/mg protein) or in the particulate fraction (38.1 vs 36.5 pmol P/min/mg protein) of the erythrocytes.
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PMID:Subcellular distribution of protein kinase C (pKC) in erythrocytes and concentration of D-myo-inositol-1,4,5-trisphosphate (IP3) in platelets and monocytes of force-fed zinc-deficient rats. 886 51


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