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)

We recently reported that phospholamban, the activator of the cardiac sarcoplasmic reticulum calcium pump, is phosphorylated by both cAMP-dependent protein kinase and a membrane-bound, Ca2+/calmodulin-dependent phospholamban kinase. Phospholamban kinase and glycogen phosphorylase b kinase share the same substrate specificity. They differ however in that phospholamban kinase exhibits an absolute requirement for exogenous calmodulin. In line with the latter observation, phospholamban kinase is shown in this report to be inhibited by fluphenazine. Lower concentrations of the drug induced an activation of the kinase, presumably by hydrophobic interaction with either membrane phospholipids or integral proteins. Also, phospholamban kinase was found to be totally insensitive to antibodies elicited against phosphorylase kinase. Since antipsychotic drugs fail to inhibit the delta-subunit-dependent activity of phosphorylase kinase, the above findings confirm that the two kinases are distinct molecular entities. After detergent solubilization of the sarcoplasmic reticulum, the phospholamban-ATPase complex remains a substrate for phospholamban kinase activity, which retains the ability to catalyze the phosphorylation of exogenous phosphorylase b. However, the Ca2+ dependence is entirely lost upon solubilization and no kinase activity is retained on calmodulin-Sepharose in the presence of Ca2+ ions. Phospholamban and phosphorylase kinase activities copurify with the pump-phospholamban complex upon fractionation of the solubilized proteins by density gradient ultracentrifugation, suggesting a tight interaction between the ATPase, its activator, and the phospholamban kinase. A tentative schematic representation of this supramolecular assembly is based upon the results described in this and preceding papers.
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PMID:Ca2+/calmodulin-dependent phospholamban kinase from cardiac sarcoplasmic reticulum is distinct from phosphorylase kinase and forms a regulatory complex with phospholamban and the Ca2+-ATPase. 622 Jun 53

Liver glycogen phosphorylase associated with the glycogen pellet was activated by a MgATP-dependent process. This activation was reduced by 90% by ethylene glycol bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid, not affected by the inhibitor of the cAMP-dependent protein kinase, and increased 2.5-fold by the catalytic subunit of cAMP-dependent protein kinase. Low levels of free Ca2+ (8 x 10(-8) M) completely prevented the effects of the chelator. The activation of phosphorylase by MgATP was shown not to be due to formation of AMP. DEAE-cellulose chromatography of the glycogen pellet separated phosphorylase from phosphorylase kinase. The isolated phosphorylase was no longer activated by MgATP in the presence or absence of the catalytic subunit of cAMP-dependent protein kinase. The isolated phosphorylase kinase phosphorylated and activated skeletal muscle phosphorylase b and the activation was increased 2- to 3-fold by the catalytic subunit of cAMP-dependent protein kinase. Mixing the isolated phosphorylase and phosphorylase kinase together restored the effects of MgATP and the catalytic subunit of cAMP-dependent protein kinase on phosphorylase activity. These findings demonstrate that the phosphorylase kinase associated with liver glycogen has regulatory features similar to those of muscle phosphorylase kinase.
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PMID:Activation of endogenous phosphorylase kinase in liver glycogen pellet by cAMP-dependent protein kinase. 624 74

Diaphragm extracts were subjected to electrophoresis on polyacrylamide gels to separate the different molecular species of th cyclic AMP-dependent protein kinase. Using cyclic [3H]AMP, three peaks of binding activity were observed. The peak closest to the origin (peak I) was associated with cyclic AMP-dependent protein kinase activity and was abolished by incubation of the extracts with cyclic AMP prior to electrophoresis. The peak farthest from the origin (peak III) was devoid of kinase activity and was increased by incubation of extracts with cyclic AMP before electrophoresis; furthermore, when extracts were incubated with cyclic [3H]AMP before electrophoresis, essentially all the radioactivity appeared in peak III. Peak II, in an intermediate position, was also abolished by preincubation of the extracts with cyclic AMP and both its binding capacity and cyclic AMP-dependent protein kinase activity were lower than in Peak I. A peak of cyclic AMP-independent protein kinase (peak 0) that migrated more slowly than peak II was also detected. From these and other data it is concluded that peaks I and II are cyclic AMP-dependent protein kinase and that peak III is the dissociated regulatory subunit, respectively. Peak 0 is cyclic AMP-independent protein kinase together with free catalytic subunits from cyclic AMP-dependent protein kinase. Incubation of rat diaphragms with epinephrine resulted in dose- and time-dependent decrease in peak I and increase in peak III. These changes correlated with the decrease of cyclic AMP-dependent protein kinase associated with peak I. No changes in Peak II were observed with epinephrine, but an increased peak 0 was noted. Changes in peak I and peak III correlated with the modification of glycogen synthase and glycogen phosphorylase activities. No regulatory subunits (peak III) were detected as phosphorylated forms in diaphragms previously equilibrated with 32P. Treatment with epinephrine produce no noticeable phosphorylation of these regulatory subunits.
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PMID:Epinephrine effects on cyclic AMP-dependent protein kinases from rat diaphragms. 625 Jun 36

The ability of acetylcholine to antagonize catecholamine-induced activation of myocardial cyclic AMP dependent protein kinase and glycogen phosphorylase activity was assessed using isolated perfused rat hearts. Perfused hearts were treated with either saline, epinephrine, epinephrine plus phentolamine or isoproterenol. After 1 minute of infusion of the indicated drug a second infusion containing acetylcholine was started. After an additional minute hearts were frozen and analyzed for cyclic nucleotide content and enzyme activity. In the presence of the alpha receptor blocking agent, phentolamine, epinephrine is a more effective activator of protein kinase than in its absence. Under these conditions the antagonistic action of acetylcholine on protein kinase activation is more pronounced. In the presence of epinephrine plus phentolamine or in the presence of isoproterenol the antagonistic action of acetylcholine on phosphorylase activity can be accounted for by a reduction in cyclic AMP-protein kinase. This same action of acetylcholine on epinephrine-stimulated phosphorylase in the aabsence of phentolamine, however, cannot be totally accounted for by a reduction in cyclic AMP content or in protein kinase activity.
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PMID:Interaction between alpha and beta adrenergic receptors and cholinergic receptors in isolated perfused rat heart: effects on cAMP-protein kinase and phosphorylase. 625 Nov 20

Graded doses of ochratoxin A incorporated into the diet (0, 0.5, 1.0, 2.0, 4.0, and 8.0 micrograms/g) of broiler chickens significantly (P < 0.05) inhibited activity of protein kinase, the initiator enzyme of the glycogen phosphorylase system, in the livers at all dose levels. Only the highest dose, 8.0 micrograms/g, significantly reduced the total activity of phosphorylase kinase, which is activated by protein kinase. The total activity of phosphorylase, which is activated by phosphorylase kinase, was unaltered by ochratoxin A at any level. Additon of ochratoxin A to liver extracts control birds inhibited protein kinase but not phosphorylase kinase. When added to extracts of livers from control birds, cyclic adenosine 3',5'-monophosphate stimulated protein kinase but not phosphorylase kinase. The cyclic adenosine 3',5'-monophosphate had no effect when added to extracts from birds fed ochratoxin A. These results suggest that ochratoxin A affects primarily the cyclic adenosine 3',5'-monophosphate-dependent protein kinase which initiates the enzymatic cascade leading to glycogenolysis. Furthermore, these results conform an earlier assignment on morphological criteria of the glycogenosis of ochratoxicosis as a type X glycogen storage disease.
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PMID:Inhibition of the glycogen phosphorylase system during ochratoxicosis in chickens. 625 38

This study was initiated to determine whether glycogen phosphorylase activation was defective in hearts of alloxan diabetic rats. When hearts were perfused by gravity flow for 1 to 10 min with various concentrations of epinephrine, activation of glycogen phosphorylase in the diabetic was significantly greater at every time and epinephrine concentration than that seen in the normal. Cyclic AMP accumulation and protein kinase activation by epinephrine in the diabetic were not appreciably different or were lower than the normal responses to the hormone. The effects of epinephrine on cAMP and protein kinase were blocked in both normal and diabetic hearts by propranolol. While the beta blocker prevented phosphorylase activation in the normal hearts, it did not block phosphorylase activation by epinephrine in the diabetic hearts. Likewise, the alpha agonist phenylephrine activated phosphorylase in the diabetic but not in the normal hearts. While glucagon produced the same phosphorylase hypersensitivity in diabetic hearts, the cAMP and protein kinase responses were not altered by diabetes. Phosphorylase phosphatase activity was found to be unaltered by either epinephrine or diabetes, whereas phosphorylase kinase activation by epinephrine in the diabetic was double the normal response. These data are consistent with a diabetes-related unmasking of an alpha effect on cardiac phosphorylase activation and an unexplained increase in the sensitivity of phosphorylase kinase activation by protein kinase.
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PMID:A hypersensitivity of glycogen phosphorylase activation in hearts of diabetic rats. 625 85

Perfusion of livers from fed rats with medium containing glucagon (2 x 10(-10) or 1 x 10(-8) M) resulted in both time- and concentration-dependent inactivation of glycogen synthase phosphatase. Expected changes occurred in cAMP, cAMP-dependent protein kinase, glycogen synthase, and glycogen phosphorylase. The effect of glucagon on synthase phosphatase was partially reversed by simultaneous addition of insulin (4 x 10(-8) M), an effect paralleled by a decrease in cAMP. Addition of arginine vasopressin (10 milliunits/ml) resulted in a similar inactivation of synthase phosphatase and activation of phosphorylase, but independent of any changes in cAMP or its kinase. Phosphorylase phosphatase activity was unaffected by any of these hormones. Synthase phosphatase activity, measured as the ability of a crude homogenate to catalyze the conversion of purified rat liver synthase D to the I form, was no longer inhibited by glucagon or vasopressin when phosphorylase antiserum was added to the phosphatase assay mixture in sufficient quantity to inhibit 90-95% of the phosphorylase a activity. These data support the following conclusions: 1) hepatic glycogen synthase phosphatase activity is acutely modulated by hormones, 2) hepatic glycogen synthase phosphatase and phosphorylase phosphatase are regulated differently, 3) the hormone-mediated changes in synthase phosphatase cannot be explained by an alteration of the synthase D molecule affecting its behavior as a substrate, and 4) glycogen synthase phosphatase activity is at least partially controlled by the level of phosphorylase a.
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PMID:Hormonal regulation of hepatic glycogen synthase phosphatase. 625 45

Human polymorphonuclear leucocytes were found to respond to activation by immunoglobulin opsonized latex particles and to complement opsonized zymosan particles with a rapid transient increase in cAMP concentration, dissociation of the cAMP dependent protein kinase, activation of glycogen phosphorylase and glycogen break down. However, since phosphorylase kinase was not activated, the activation of phosphorylase is believed to be secondary to non-covalent activation of phosphorylase kinase by Ca2+. Activation by the soluble stimulator phorbol myristate acetate resulted in activation of phosphorylase and glycogen break down, whereas no changes in cAMP concentration, protein kinase activity, or phosphorylase kinase activity were observed. The activation of phosphorylase is ascribed to an increase in cytosolic Ca2+ concentration. The response to stimulation by zymosan was strongly inhibited by ethylene glycol-bis-(beta-aminoethyl ether)-N,N1-tetraacetic acid, which did not affect stimulation by either latex particles or phorbol myristate acetate. The same differential effect of ethylene glycol-bis(beta-aminoethyl ether)-N,N1-tetraacetic acid was observed when the response of the cells was measured as increase in oxygen consumption and activation of the hexose monophosphate shunt.
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PMID:Activation of the glycogenolytic cascade in human polymorphonuclear leucocytes by different phagocytic stimuli. 627 56

Livers isolated from both fed normal and alloxan diabetic rats were perfused for 30 min using Krebs-Henseleit bicarbonate blood buffer medium followed by 10 min flow-through infusions with either 5 mM or 28 mM fructose concentrations. In livers of normal and diabetic rats, both 5 mM and 28 mM fructose concentrations produced an elevation in tissue cyclic AMP levels, activation of glycogen phosphorylase, increased protein kinase activity, decreased tissue ATP levels, large increases in tissue fructose-1-phosphate, and variable effects upon glycogen synthase. These results are consistent with previously reported cyclic AMP mediated activation of glycogen phosphorylase by fructose via protein kinase in normal rat liver. In addition, both 5 mM and 28 mM fructose infusion resulted in large decreases in normal and diabetic synthase phosphatase activity. Therefore, these results in both normal and diabetic livers are inconsistent with a direct beneficial effect of fructose in the isolated perfused rat liver.
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PMID:Adverse effects of fructose in perfused livers of diabetic rats. 628 12

The effects of levamisole on muscle contraction and glycogen metabolism have been examined in isolated muscle-cuticle sections of the roundworm Ascaris suum. Muscle contraction occurred when various levels of levamisole were perfused through the preparation. At a levamisole concentration of 0.42 mM, the period of contraction lasted only about 6 min and was followed by a period of relaxation. During this relaxation period, there was an activation of glycogen synthase (EC 2.4.1.11), as evidenced by a decrease in the Ka values of glucose 6-phosphate for glycogen synthase to 0.26 mM from control values of 0.50 mM. The glycogen phosphorylase (EC 2.4.1.1) activity ratio decreased from 0.85 to 0.65, which indicated an inactivation of this enzyme. Concomitant with this activation of glycogen synthase and inactivation of phosphorylase there was an increased synthesis of glycogen. In addition, the presence of levamisole prevented both the serotonin-induced cyclic AMP accumulation and the activation of the cyclic AMP-dependent protein kinase (EC 2.7.1.37). However, levamisole did not significantly affect the changes in glycogen synthase and phosphorylase brought about by perfusion with the neurostimulator acetylcholine. Collectively, the data indicated that levamisole caused a transient muscle contraction followed by muscle relaxation, and the muscle relaxation effect appeared to be the result of a levamisole-inhibited cyclic AMP-mediated pathway of glycogen utilization.
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PMID:The role of cyclic AMP-mediated regulation of glycogen metabolism in levamisole-perfused Ascaris suum muscle. 630 Jun 47


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