EC:2.7.11.13 - FACTA Search

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)

Short term regulation of hepatic cholesterol ester hydrolase by reversible phosphorylation is described. Two different kinase systems seem to be involved in this regulation. The addition of ATP, cyclic AMP and Mg2+ to rat liver 104,000 X g supernatant (S104) produced a 100-140% increase in cholesterol ester hydrolase activity. This stimulation was abolished when protein kinase inhibitor was added prior to the addition of ATP, cyclic AMP and Mg2+. Cholesterol ester hydrolase activity was also stimulated when calcium ions, phosphatidylserine, and diolein were added to S104 along with ATP and Mg2+. Diolein in this reaction could be substituted by phorbol 12-myristate 13-acetate. Preincubation of S104 with alkaline phosphatase resulted in a deactivation of cholesterol ester hydrolase. The addition of increasing concentrations of Mg2+ to S104 produced increasing inhibition of cholesterol ester hydrolase activity, and this effect was blocked by NaF. It is suggested that rat liver cholesterol ester hydrolase is activated by cyclic AMP dependent protein kinase and protein kinase C. Deactivation is accomplished by dephosphorylation catalyzed by a phosphoprotein phosphatase, dependent on Mg2+.
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PMID:Activation of rat liver cholesterol ester hydrolase by cAMP-dependent protein kinase and protein kinase C. 255 47

The roles of calcium, cyclic AMP (cAMP), activation of protein kinase C (PKC) and the effect of ATP on glucagon secretion were investigated in intact and permeabilized rat islets of Langerhans, Ca2+ (10 nM-10 microM) stimulated glucagon secretion from electrically permeabilized islets in a dose-dependent manner. Forskolin and cAMP stimulated secretion from intact and permeabilized islets respectively, the latter at both sub-stimulatory (50 nM) and stimulatory (10 microM) Ca2+ concentrations. The tumour-promoting phorbol ester phorbol 12-myristate 13-acetate (PMA) increased secretion from both intact and permeabilized islets. In the latter, PMA increased glucagon release at both Ca2+ concentrations, the effect being enhanced at the stimulatory Ca2+ concentration, over and above that caused by Ca2+ alone. Reduction of ATP content by incubation with the metabolic inhibitor 2,4-dinitrophenol resulted in an increased basal release of glucagon from intact islets, whilst arginine-induced glucagon secretion was abolished in both intact and permeabilized islets. Ca2+-induced glucagon secretion required MgATP in the permeabilized islets of Langerhans. These results suggest that Ca2+ acts as an initiator of glucagon secretion, whilst cAMP and activation of PKC may exert their effect as modulators of secretion. ATP is required for glucagon secretion in electrically permeabilized islets and is necessary for arginine-induced glucagon secretion in both intact and permeabilized islets.
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PMID:Role of intracellular mediators in glucagon secretion: studies using intact and electrically permeabilized rat islets of Langerhans. 285 94

The effects of adenosine, adenosine deaminase (ADA), and an irreversible ADA inhibitor 2'-deoxycoformycin (DCF) on granulocyte aggregation in response to four different stimuli: the synthetic chemotaxin N-formyl-met-leu-phe (FMLP), zymosan-activated plasma (ZAP), the calcium ionophore A23187, and phorbol myristate acetate (PMA) were studied. Adenosine inhibited granulocyte aggregation in response to 10(-7) mol/L FMLP in a dose-dependent fashion; inhibition in the presence of 1 mumol/L adenosine was 25% +/- 3% (SD) and was 50% (the maximal inhibition observed) with 1 mmol/L adenosine. Quantitatively similar results were obtained when ZAP or A23187 was used as the aggregant but the response to PMA was not affected. ADA not only reversed the inhibition due to adenosine but actually augmented the aggregation to FMLP by 118% +/- 9%. Similar results were obtained with ZAP and A23187 but not with PMA. These effects of ADA depended on its enzymatic activity as they could be blocked by preincubation with DCF. Fluorescent measurement of intracellular calcium in fura-2 loaded granulocyte suspensions established that neither adenosine nor ADA affected subsequent FMLP-stimulated calcium responses. Adenosine, therefore, may inhibit granulocyte responsiveness by blocking signal transduction at a point after calcium entry/mobilization but before activation of protein kinase C. Furthermore, the augmentation of responses seen with ADA suggests that endogenous adenosine may be a physiologic autocrine regulator of granulocyte function.
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PMID:Endogenous and exogenous adenosine inhibit granulocyte aggregation without altering the associated rise in intracellular calcium concentration. 326 May 24

Analysis of the cytosol fraction containing protein kinase C activity from rabbit peritoneal neutrophils by DEAE-cellulose chromatography identified protein kinase C activity in the fractions eluted with 0.08 M-0.14 M NaCl and protein kinase C inhibitor activity in the fraction eluted with 0.16 M-0.5 M NaCl. On further analysis by Sephadex G-150 gel filtration, one peak of protein kinase C and two peaks of inhibitor activity were identified. The peak of protein kinase C and two peaks of inhibitor activity were identified. The peak of protein kinase C activity eluted at Ve/Vo 1.6 corresponding to a Stokes radius of 35 A. The first peak of the inhibitor activity eluted at Ve/Vo 1.4 and the second peak of the inhibitor activity eluted at Ve/Vo 2.5. The peak of phosphoprotein phosphatase activity does not coincide with the peaks of inhibitor activity of protein kinase C.
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PMID:Partial characterization of protein kinase C and inhibitor activity of protein kinase C in rabbit peritoneal neutrophils. 345 58

We have developed a cell-free assay to detect and characterize nerve growth factor (NGF)-activated protein kinase activity. Cultured PC12 cells were briefly exposed to NGF, and extracts of these were assayed for phosphorylating activity using exogenously added tyrosine hydroxylase as substrate. Tyrosine hydroxylase was employed since it is an endogenous substrate of NGF-regulated kinase activity and is activated by phosphorylation. In the cell-free assay, extracts prepared from NGF-treated cells yielded a 2-3-fold greater incorporation of phosphate into tyrosine hydroxylase as compared with extracts of control, NGF-untreated cells. Activation did not occur, however, if NGF was added directly to cell extracts. The NGF-stimulated phosphorylating activity appeared to be due to regulation of a protein kinase rather than of a phosphoprotein phosphatase. Characterization of the kinase (designated as kinase N) showed that it is soluble, is detectably activated within 1-3 min after cells are exposed to NGF and maximally activated by 10 min, is half-maximally activated with 0.5 nM NGF and maximally activated with 1 nM NGF, is detectable in the presence of either Mg2+ or Mn2+ but does not require Ca2+, does not require nonmacromolecular cofactors, can use histone H1 as a substrate, and exhibits a 2-fold increase in apparent Vmax in response to NGF but does not undergo a significant change in apparent Km for either ATP or GTP. A number of characteristics of kinase N were assessed including susceptibility to inhibitors, substrate specificity, cofactor requirements, ATP dependence, and lack of down-regulation by prolonged expose to a phorbol ester. These studies indicated that it lacks tyrosine kinase activity and is distinct from a variety of well-characterized protein kinases including cAMP-dependent protein kinase, protein kinase C (Ca2+/phospholipid-dependent enzyme), Ca2+/calmodulin-dependent kinase, and casein kinase II. Preliminary purification data show that the kinase has a basic pI and that it has an apparent Mr of 22,000-25,000. The only amino acid in tyrosine hydroxylase found to be phosphorylated by the semipurified kinase is serine.
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PMID:Cell-free detection and characterization of a novel nerve growth factor-activated protein kinase in PC12 cells. 358 24

The role of phosphoprotein phosphatase in the regulation of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in rat pinealocytes was investigated using the three phosphatase inhibitors calyculin A, tautomycin, and okadaic acid. Calyculin A (0.1 microM) was found to enhance the isoproterenol- and norepinephrine-stimulated cAMP accumulation six- and threefold, respectively, whereas tautomycin and okadaic acid were less effective. The effect of calyculin A was rapid (within 5 min) and persisted in the presence of phosphodiesterase inhibition. However, in contrast to protein kinase C activation or intracellular calcium elevation, the phosphatase inhibitors were less effective in potentiating the cAMP response stimulated by forskolin or cholera toxin, and their effects were not blocked by calphostin C or N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide. The adrenergic-stimulated cGMP response was also less sensitive to the phosphatase inhibition. Therefore, our results suggest that 1) the adrenergic-stimulated cAMP signal is subjected to the tonic inhibition by phosphoprotein phosphatase; 2) phosphatase inhibitors enhance cAMP synthesis through their actions at the receptor level; and 3) the cAMP signal is more sensitive to the regulation by phosphorylation than cGMP in rat pinealocytes.
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PMID:Phosphatase inhibitors potentiate adrenergic-stimulated cAMP and cGMP production in rat pinealocytes. 753 89

To verify the hypothesis of Na-K-Cl cotransport (COTR) involvement in ion transport abnormalities as revealed in vascular smooth muscle cells (VSMC) of spontaneously hypertensive rats (SHR), we compared the rate of ouabain-insensitive, bumetanide-inhibited 86Rb influx in quiescent and growing cultures of VSMC from the aorta of SHR and normotensive (BN.lx) rats and its regulation by the cAMP signaling system. Basal COTR was not altered in quiescent cells from SHR but was decreased by 30% to 40% (P < .02) in growing SHR VSMC as compared to BN.lx rats. In quiescent BN.lx VSMC, isoproterenol inhibited COTR by 50% and induced cell shape transition of > 90% of cells, resulting in the appearance of rounded VSMC with arborized cytoplasms. In contrast, isoproterenol elicited cell shape transition in only 50% of quiescent SHR VSMC and did not modify COTR. In growing cells, it decreased COTR by 85% to 95% and altered cell morphology in > 95% of VSMC without differences between SHR and BN.lx rats. Neither inhibitors of protein kinase A (H-89 and KT-5720) nor an inhibitor of phosphoprotein phosphatase (okadaic acid) affected cell shape transition and COTR suppression in isoproterenol-treated VSMC. The COTR suppression and cytoplasm arborization was also demonstrated by the addition of cytochalasin B, a disintegrator of microfilament bundles, and staurosporine, an inhibitor of protein kinase C. The effects of these compounds on COTR and SHR and BN.lx VSMC morphology were not different. The calmodulin antagonist R24571 decreased COTR by 60% to 70% in quiescent BN.lx VSMC and did not modify this carrier in SHR VSMC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered beta-adrenergic regulation of Na-K-Cl cotransport in cultured smooth muscle cells from the aorta of spontaneously hypertensive rats. Role of the cytoskeleton network. 754 1

The Saccharomyces cerevisiae gene PPZ1 codes for a 692-residues protein that shows in its carboxyl-terminal half about 60% identity with the catalytic subunit of mammalian and yeast protein phosphatase-1 and that is involved in salt homeostasis. The complete PPZ1 protein has been successfully expressed as a soluble glutathione-S-transferase fusion protein. The recombinant protein, after purification by a single affinity chromatography step, displayed phosphatase activity towards a number of substrates, including myelin basic protein, histone 2A and casein, but was ineffective in dephosphorylating glycogen phosphorylase. It was also active towards p-nitrophenylphosphate. The activity was severalfold increased by the presence of Mn2+ ions and by limited trypsinolysis. The enzyme was inhibited by okadaic acid and microcystin-LR at concentrations comparable to what is found for type 1 protein phosphatase although it was much less sensitive to inhibitor-2. The recombinant protein was phosphorylated in vitro by cAMP-dependent protein kinase, protein kinase C and casein kinase-2. Phosphorylation affected preferentially sites located in the amino-terminal half of the protein and did not alter the activity of the phosphatase.
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PMID:Biochemical characterization of recombinant yeast PPZ1, a protein phosphatase involved in salt tolerance. 761 85

We have used quail skeletal myotubes expressing a temperature-sensitive allele of the v-src oncogene to address the issue of the homeostasis of sarcomeric myofibrils in differentiated muscle cells. Reactivation of the v-Src tyrosine kinase by shifting the cultures to the permissive temperature leads within minutes to the formation of F-actin-containing bodies (ABs), that originate in the ventral region of the myotubes and increase in number concomitantly with the dismantling of the I-Z-I complex of the sarcomeres. This process is detailed by confocal and electron microscopy. Indirect immunofluorescence reveals that ABs contain muscle-specific protein isoforms associated with the I-Z-I complexes and vinculin, a component of the cytoskeletal network. Anti-phosphotyrosine antibodies label proteins in ABs and Z-discs. Evidence is presented indicating that this phenomenon specifically depends on the persistent activation of v-Src, rather than on a general increase in phosphotyrosine content such as that induced by vanadate. AB formation is prevented by activation of protein kinase C by phorbol ester or by treatment with the kinase inhibitor 2-aminopurine, without any detectable effect on tyrosine phosphorylation. Taken together these findings indicate that phosphorylation of specific target proteins by v-Src, although necessary, is not sufficient per se to induce AB formation. In addition, the signal transduction cascade that culminates in MAP kinase activation and its nuclear translocation is activated both by v-Src and phorbol ester, and is relatively unaffected by 2-aminopurine. These findings imply that both phorbol esters and 2-aminopurine operate, at least in part, at the level of alternative pathways that may diverge upstream of the MAP kinase and are presumably mediating the early effects of v-Src on the differentiated phenotype.
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PMID:Maintenance of the differentiated state in skeletal muscle: activation of v-Src disrupts sarcomeres in quail myotubes. 764 4

Studies were performed to determine the primary signal transduction mechanism that mediates adenosine stimulation of electrogenic sodium transport in renal epithelial cells. Experiments were performed on cultured amphibian A6 cells with an adenosine analogue that preferentially binds to the A1 receptor, cyclohexyladenosine (CHA). Sodium transport was assessed by the equivalent short circuit current (Ieq). CHA was found to stimulate Ieq via activation of an A1 receptor because (1) the threshold concentration was 1 nM compared to that of 10 microM for the specific A2 agonist CGS21680, (2) CHA inhibited vasopressin (AVP)-stimulated cAMP production by a pertussis toxin-sensitive mechanism, and (3) the action of CHA was inhibited by the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). CHA increased intracellular Ca2+ ([Ca2+]i) and stimulated phosphoinositide turnover at concentrations that increased Ieq and in a time course that paralleled the increase in Ieq. Ion transport was stimulated by a Ca(2+)-dependent mechanism because the CHA induced increase in Ieq was inhibited by chelating [Ca2+]i with 5,5'dimethyl BAPTA in a dose-dependent manner, with a Ki of approximately 10 microM. The increase in Ieq was also dose-dependently inhibited by the specific PKC inhibitors dihydroxychlorpromazine and chelerythrine, and by trifluoperazine which inhibits PKC and calmodulin. Further studies indicated that CHA-stimulated Ieq was independent of cAMP generation because CHA did not induce an increase in cAMP accumulation parallel to the increase in Ieq in a dose-response analysis, and the adenylate cyclase inhibitor 2',5' dideoxy-adenosine (DDA) did not affect the CHA-induced increase in Ieq.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine stimulation of Na+ transport is mediated by an A1 receptor and a [Ca2+]i-dependent mechanism. 764 26

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