Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ca2+/phospholipid-dependent protein kinase (PKC) was inhibited by sulphated polysaccharides. Pentosan polysulphate (PPS) and heparin were 8-10-times more potent than dextran sulphate or heparan sulphate. Steady-state studies revealed that PPS was a competitive inhibitor with respect to ATP with an apparent Ki value of 0.32 micrograms/ml and a non-competitive inhibitor with respect to histones. In contrast, the inhibition of PKC by heparin was competitive with substrate and non-competitive with respect to ATP. The interaction of sulphated polysaccharides with the catalytic domain of PKC was further demonstrated by the absence of effect on [3H]phorbol 12,13-dibutyrate binding to the regulatory domain of PKC. Furthermore, PPS and heparin inhibited equally cAMP-dependent protein kinase and tyrosine protein kinase. Structure-function relationships indicated that the Inhibition of protein kinases by PPS and heparin fractions was highly dependent on molecular weight. Additionally, PKC-affinity chromatography revealed that a high-molecular-weight heparin fraction with strong anti-PKC activity was eluted. We set out to demonstrate that heparin and PPS, which are potent antiproliferative agents on vascular smooth muscle cells (SMC), alter intracellular PKC activity (both membrane and cytosolic). Therefore, it is suggested that the mechanism by which sulphated polysaccharides inhibit SMC growth may be by direct inhibition of PKC in SMC.
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PMID:Effect of pentosan polysulphate, standard heparin and related compounds on protein kinase C activity. 170 25

The delta-subunit of the nicotinic acetylcholine receptor from Torpedo californica electric tissue isolated form receptor purified in the absence of protein phosphatase inhibitors contains a total of four phosphate groups. Three of these are shown to represent phosphoserine groups. The fourth possible represents phosphotyrosine. The phosphate groups are localized within the primary structure: We found phosphoserine in positions delta S361 and delta S377, the predicted sites phosphorylated by PKA and PKC, respectively. In addition, we found that position delta S362 is also phosphorylated. Phosphorylation experiments with the synthetic peptide delta L357-delta K368 show that phosphorylation of this novel site can be catalyzed by PKA and by PKC. It is concluded that the delat-subunit of the acetylcholine receptor is stably and not transiently phosphorylated. Implications for the physiological functions of receptor phosphorylation are discussed.
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PMID:Phosphorylation sites of the nicotinic acetylcholine receptor. A novel site detected in position delta S362. 170 13

The phosphorylation of epithelial-specific cytokeratin (CK) 8 and 18 was studied in the human colonic cell line HT29. Metabolic labelling of cells with orthophosphate resulted in phosphorylation of cytokeratins 8/18 on serine residues. When phorbol acetate was added to labelled cells, a 2.2-fold increase in CK8/18 phosphate labelling was noted, whereas increasing intracellular cAMP levels using forskolin or 8-Br-cAMP showed no significant change in CK phosphorylation. CKs8/18 were also phosphorylated by added PKC in the presence of [gamma-32P]ATP. Tryptic peptide map analysis of the phosphorylated CK8 species showed that treatment of cells with 8-Br-cAMP or phorbol acetate generated a phosphopeptide not seen in control cells. In contrast, tryptic peptide maps of phosphorylated CK18 showed no discernable differences. Our results support a role for PKC in the phosphorylation of epithelial cytokeratins, with some phosphorylation sites being modulated by cAMP dependent protein kinase.
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PMID:Phorbol acetate enhances the phosphorylation of cytokeratins 8 and 18 in human colonic epithelial cells. 170 19

The secretion of fluid into the airway lumen is due in part to active chloride secretion across the epithelium. Changes in Cl secretion require coordinated changes in the turnover of several transport proteins in order to avoid lethal changes in cell volume. Several different Ca- and cAMP-dependent pathways effect this coordination. Many mediators raise cyclic AMP which activates protein kinase A which in turn opens the apical membrane Cl channel. Cyclic AMP also raises Cai (without change in levels of inositol triphosphate, IP3), and this Ca is probably responsible for activation of basolateral K channels and NaK2Cl cotransporters. Other mediators raise Cai by elevating IP3, and seem to stimulate chloride secretion entirely by Ca-dependent pathways with no change in cyclic AMP levels. Protein kinase C and arachidonic acid inhibit Cl secretion.
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PMID:Regulation of airway mucosal ion transport. 171 99

Expression of the urokinase-type plasminogen activator (uPA) gene in LLC-PK1 cells can be induced by signals mediated by both cAMP-dependent protein kinase (PKA) and Ca(2+)- and phospholipid-dependent protein kinase (PKC). We have utilized the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) to down-regulate PKC, in order to test for an effect on the PKA-mediated induction of the uPA gene expression. Incubation of cells for 24 h with 100 ng/ml TPA caused a marked decrease of PKC protein, both in cytosolic and particulate fractions, and an 85% reduction of total PKC activity. After down-regulation of PKC, uPA mRNA accumulation induced by 8-Br-cAMP was 5-10-fold higher than in control cells. Both uPA mRNA stability and uPA gene transcription rates induced by 8-Br-cAMP were increased by PKC down-regulation (6- and 1.8-fold, respectively). Although total PKA activity was reduced by 20% in extracts from PKC-depleted cells, activation of PKA by 8-Br-cAMP was 2.5-fold higher than in control cells. This enhanced activation of PKA in PKC-depleted cells also occurred in response to other cAMP derivatives and to cAMP induced endogenously by the activation of adenylate cyclase with forskolin, but was not due to down-regulation-associated changes in the rate of cAMP synthesis. Our results demonstrate that in LLC-PK1 cells, down-regulation of PKC results in an enhanced induction of uPA gene expression by cAMP-mediated signals without alterations in adenylate cyclase activity, suggesting a mechanism distal to adenylate cyclase.
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PMID:Protein kinase C down-regulation enhances cAMP-mediated induction of urokinase-type plasminogen activator mRNA in LLC-PK1 cells. 171 70

Protein kinase C (PKC) is routinely assayed, after it is partially purified over DEAE-cellulose chromatography to eliminate any interfering protein kinases and phosphatases, by measuring the transfer of gamma-phosphate of [gamma-32P]ATP to H1 histone. Recently, it has been shown that a synthetic peptide, comprising residues 4-14 of myelin basic protein (MBP4-14), is a very selective PKC substrate which is not phosphorylated effectively by cyclic AMP-dependent protein kinase, casein kinase I and II, Ca2+/calmodulin dependent protein kinase II or phosphorylase kinase [Yasuda, I., Kishimoto, A., Tanaka, S-I., Tominaga, M., Sakurai, A. and Nishizuka, Y. (1990) BBRC 166, 1220-1227]. We report here that once MBP4-14 is phosphorylated, it is not dephosphorylated by okadaic acid-sensitive phosphatases (protein phosphatases 1, 2A and 3) or other protein phosphatases such as calcineurin and/or PP 2C present in hippocampal homogenates. Therefore, MBP4-14 can be used for PKC assay in crude extracts of neural tissue.
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PMID:A phosphatase resistant substrate for the assay of protein kinase C in crude tissue extracts. 171 69

Calcium-calmodulin dependent protein kinase II (CaM-KII) has been implicated in the inhibition of Na(+)-H+ exchange activity in the brush border of the renal proximal convoluted tubule. Conversely, the activity of the antiporter is stimulated in response to phosphorylation by calcium-phospholipid dependent protein kinase (PKC). In these experiments, we explored the potential for direct interaction between these two protein kinases by determining the effect of PKC activation by tumor promoting phorbol esters on the expression of mRNA for CaM-KII in the rabbit renal proximal tubule. The results indicate that activation of PKC reduced the steady-state levels of the mRNA for the alpha subunit of CaM-KII in a dose and time dependent manner. This suggests a novel mechanism by which PKC can antagonize the action of CaM-KII in selected tissues.
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PMID:The effect of phorbol esters on the expression of mRNA for the alpha subunit of calcium/calmodulin dependent protein kinase II in rabbit renal proximal tubules. 172 Jan 72

Protein kinase C is a family of multifunctional protein serine/threonine kinase and generally accepted to be involved in a wide variety of cellular signal transduction. Biochemical and immunochemical studies as well as sequence analysis of its cDNA clones have revealed the existence of multiple subspecies of this enzyme with obvious tissue-specific expression. Enzymatic properties of type I, II, and III protein kinase C subspecies, which are encoded by gamma-, beta I- and beta II, and alpha-cDNA, respectively, are well characterized. Many proteins and peptides are reported as phosphate acceptors of these protein kinase C subspecies. In this study, it is shown that a synthetic peptide, Gln-Lys-Arg-Pro-Ser-Gln-Arg-Ser-Lys-Tyr-Leu, which corresponds to amino acid residues 4-14 of bovine myelin basic protein, is the most specific and convenient substrate for selective assay of protein kinase C among various phosphate acceptor proteins and peptides. This peptide is phosphorylated at Ser-8, but not Ser-11 by protein kinase C subspecies in a manner dependent on Ca2+, phosphatidylserine, and diacylglycerol. This peptide is not phosphorylated by other protein serine/threonine kinases such as cyclic AMP-dependent protein kinase. Thus, it is possible to assay protein kinase C activity in the crude tissue extracts selectively using this peptide as a phosphate acceptor.
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PMID:Selective assay of protein kinase C with a specific peptide substrate. 172 Aug 27

The PKC1 gene of Saccharomyces cerevisiae encodes a homolog of mammalian protein kinase C that is required for yeast cell growth and division. To identify additional components of the pathway in which PKC1 functions, we isolated extragenic suppressors of a pkc1 deletion mutant. All of the suppressor mutations were dominant for suppressor function and defined a single locus, which was designated BCK1 (for bypass of C kinase). A molecular clone of one suppressor allele, BCK1-20, was isolated on a centromere-containing plasmid through its ability to rescue a conditional pkc1 mutant. The BCK1 gene possesses a 4.4-kb uninterrupted open reading frame predicted to encode a 163-kDa protein kinase. The BCK1 gene product is not closely related to any known protein kinase, sharing only 45% amino acid identity with its closest known relative (the STE11-encoded protein kinase) through a region restricted to its putative C-terminal catalytic domain. Deletion of BCK1 resulted in a temperature-sensitive cell lysis defect, which was suppressed by osmotic stabilizing agents. Because pkc1 mutants also display a cell lysis defect, we suggest that PKC1 and BCK1 may normally function within the same pathway. Suppressor alleles of BCK1 differed from the wild-type gene in a region surrounding a potential PKC phosphorylation site immediately upstream of the predicted catalytic domain. This region may serve as a hinge between domains whose interaction is regulated by PKC1.
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PMID:Dominant mutations in a gene encoding a putative protein kinase (BCK1) bypass the requirement for a Saccharomyces cerevisiae protein kinase C homolog. 172 97

Protein kinase C (PKC) has a role in signal transduction during hexamethylene bisacetamide (HMBA)-induced differentiation of murine erythroleukemia cells (MELC). Separation of MELC PKC isozymes by hydroxylapatite chromatography yields a major peak (III) and a minor peak (II) of PKC activity, previously reported to contain the PKC alpha and beta isozymes, respectively. In the present study, we confirm that peak III activity is PKC alpha but show that peak II contains PKC epsilon and little or no PKC beta. Immunoblot analysis with isozyme-specific anti-alpha and anti-epsilon PKC antibodies detected PKC alpha in peak III and PKC epsilon in peak II. Peak III activity was markedly enhanced (up to 20-fold) by phosphatidylserine, diolein, and Ca2+, whereas addition of these cofactors to the reaction mixture stimulated peak II activity only 2- to 4-fold. RNase protection analysis of MELC RNA showed that PKC alpha and PKC epsilon RNAs were in a ratio of approximately 2:1, but PKC beta RNA was barely detectable. Taken together, these data indicate that MELC contain PKC alpha and PKC epsilon but little or no PKC beta.
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PMID:Protein kinase C isozymes epsilon and alpha in murine erythroleukemia cells. 172 81


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