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)

Sarcoplasmic reticulum fragments isolated from dog cardiac muscle possess a calcium-accumulating system associated with a series of enzymes linked to glycogenolysis. These enzymes include: adenylate cyclase, cyclic AMP-dependent protein kinase, phosphorylase b kinase, phosphorylase (b/a, 30/1),"debrancher" enzyme, and glycogen (0.3 to 0.7 mg/mg of protein). The sarcoplasmic reticulum preparation produced glucose 1-phosphate and glucose from either endogenous or exogenous glycogen. Both the calcium-accumulating and glycogenolytic enzymes sediment in a single peak at 33% sucrose on a linear continous sucrose density gradient, and the complex remains intact throughout repeated washing. Glycogen particles appear to be associated with the sarcoplasmic reticulum in situ as well as in the isolated microsomal fraction. The sarcoplasmic reticulum-glycogenolytic complex, monitored by a linked enzyme spectrophotometric assay, shows several features: (a) activation of phosphorylase activity to peak rate occurs over a very rapid time course which cannot be duplicated using combinations of purified enzymes; (b) activation is inhibited by protein kinase inhibitor; (c) phosphorylase b functions as in the purified form with respect to AMP (Km, 0.3 mM); (d) in the presence of limiting amounts of glycogen, optimal phosphorylase b activity in the sarcoplasmic reticulum requires the presence of debrancher, and the activity is sensitive to inhibitors of that enzyme such as Tris, which suggests the possiblity that the enzymes bear a specific structual relationship to the glycogen present. Phosphorylase b leads to a activation in the sarcoplasmic reticulum was completely resistant to ethylene glycol bis(beta-aminoethyl either)-N,N'-tetraacetic acid (EGTA). Inhibition of calcium accumulation by or release of bound calcium from sarcoplasmic reticulum by X537A (RO 2-2985) did not alter the EGTA resistance. These results suggest that cardiac sarcoplasmic reticulum is a complex organelle containing functions that may be related to excitation-contraction coupling and intermediary metabolism.
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PMID:Association of gylcogenolysis with cardiac sarcoplasmic reticulum. 0 55

The purpose of this investigation was to characterize the phosphorylation of bovine cardiac troponin by cyclic AMP-dependent protein kinase. The purified troponin-tropomyosin complex from beef heart contained 0.78 +/- 0.15 mol of phosphate per mol of protein. Analysis of the isolated protein components indicated that the endogenous phosphate was predominately in the inhibitory subunit (TN-I) and the tropomyosin-binding subunit (TN-T) of troponin. When cardiac troponin or the troponin-tropomyosin complex was incubated with cyclic AMP-dependent protein kinase and [gamma-32P]ATP, the rate of phosphorylation was stimulated by cyclic AMP and inhibited by the heat-stable protein inhibitor of cyclic AMP-dependent protein kinase. The 32P was incorporated specifically into the TN-I subunit with a maximal incorporation of 1 mol of phosphate per mol of protein. The maximal amount of phosphate incorporated did not vary significantly between troponin preparations that contained low or high amounts of endogenous phosphate. The Vmax of the initial rates of phosphorylation with troponin or troponin-tropomyosin as substrates was 3.5-fold greater than the value obtained with unfractionated histones. The rate or extent of phosphorylation was not altered by actin in the presence or absence of Ca2+. The maximal rate of phosphorylation occurred between pH 8.5 and 9.0. At pH 6.0 and 7.0 the maximal rates of phosphorylation were 13 and 45% of that observed at pH 8.5, respectively. These results indicate that cyclic AMP formation in cardiac muscle may be associated with the rapid and specific phosphorylation of the TN-I subunit of troponin. The presence of endogenous phosphate in TN-T and TN-I suggests that kinases other than cyclic AMP-dependent protein kinase may also phosphorylate troponin in vivo.
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PMID:Phosphorylation of cardiac troponin by cyclic adenosine 3':5'-monophosphate-dependent protein kinase. 1 36

Immunization of guinea pigs with bovine cardiac cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) resulted in the development of precipitating antibodies to the cAMP-binding subunit of the enzyme. Both the phosphorylated and nonphosphorylated cAMP-binding protein of the protein kinase reacted with the antiserum. A radioimmunoassay was developed that detects 10 ng of holoenzyme and permits measurement of enzyme concentrations in bovine cardiac muscle. Bovine liver, kidney, brain, and skeletal muscle contain protein kinases which are immunologically identical to those found in bovine cardiac muscle. However, the proportion of immuno-reactive enzyme activity differed for each tissue. All of the immunologically nonreactive enzyme in skeletal muscle and heart was separable from immunoreactive enzyme by chromatography on DEAE-cellulose. Rat tissues and pig heart contained protein kinase activity that crossreacted immunologically in a nonparallel fashion with bovine cardiac enzyme. These results indicate that cAMP-dependent protein kinases within and between species are immunologically heterogeneous.
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PMID:Radioimmunoassay of bovine heart protein kinase. 5 18

At least three mechanical changes characterize the response of cardiac muscle to agents that enhance cyclic AMP production. In common with other inotropic interventions, tension is augmented and the rate of tension rise is increased. The third response, acceleration of the rate of relaxation, is characteristic of the actions of beta-adrenergic agonists. These mechanical effects can be attributed to changes in (1) the amount of Ca2+ released during systole, (2) the rate of Ca2+ release at the onset of systole, and (3) the rate at which Ca2+ is reaccumulated by the sarcoplasmic reticulum at the end of systole. The ability of cyclic AMP-dependent protein kinases to phosphorylate the cardiac sarcoplasmic reticulum in vitro parallels stimulation of both Ca2+ transport and Ca2+-activated ATPase. The phosphoprotein formed in the presence of cyclic AMP and protein kinase has the chemical characteristics of a phosphoester, contains mostly phosphoserine, and has an electrophoretic mobility in SDS polyacrylamide gels that corresponds to a protein of 22,000 daltons. This 22,000-dalton protein, tentatively named phospholamban, thus differs from the acyl phosphooprotein formed by the Ca2+-transport ATPase, which as an apparent molecular weight of 90,000 to 100,000 daltons. Phospholamban has not been found in fast skeletal muscle, nor is Ca2+ transport accelerated by cyclic AMP and protein kinase in sarcoplasmic reticulum from these muslces which do not respond to beta-adrenergic agonists with accelerated relaxation. It thus appears likely that phosphorylation of phospholamban correlates both with an increased rate of Ca2+ transport by cardiac sarcoplasmic reticulum in vitro and accelerated relaxation in the intact myocardium. Preliminary findings are consistent with the view that phosphorylation of phospholamban may be related to other actions on Ca2+ fluxes brought about by agents which activate adenylate cyclase in the myocardium, but these interpretations must remain speculative pending more definitive studies.
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PMID:Control of calcium transport in the myocardium by the cyclic AMP-Protein kinase system. 16 80

Catecholamine-sensitive adenylate cyclase, cyclic nucleotide phosphodiesterase, adenosine 3', 5'-monophosphate (cyclic AMP)-dependent protein kinase, kinase substrate, and phosphoprotein phosphatase have variously been reported to be present in preparations of myocardial cellular membranes that function in the movement of Ca2+ in and out of the cell and in intracellular Ca2+ translocations, indicating that these membranees possess the equipment for the formation and destruction of cyclic Amp as well as for the initiation, effectuation, and termination of a possible membrane action of the nucleotide. It has also been observed that phosphorylation of seryl residues of protein in sarcolemma- and sarcotubule-rich myocardial subcellular fractions by cyclic AMP activated intrinsic and extrinsic protein kinases confers upon these membran structures an enhanced ability to bind or take up Ca2+ and that dibutyryl cyclic AMP, like adrenaline, produces in intact cardiac muscle simultaneous increases in contractile force and in the uptake of extracellular Ca2+. These findings are suggestive of a second messenger role of cyclic AMP in the beta-adrenoreceptor-mediated actions of catecholamines on myocardial contractile force and relaxation, in which Ca2+ would serve as a third messenger and be subject, respectively, to more effective removal from its binding sites on troponin. An alternative interpretation regards Ca2+ and cyclic AMP as interdependent twin second messengers in the catecholamine-induced inotropism. Since the physiological meaning of the reported effects of cyclic AMP on isolated myocardial membrane preparations is far from established an instances of a dissociation between the effects of catecholamines on myocardial contractile force and cyclic AMP levels have been observed, there is still room for hypotheses that relegate cyclic AMP to a nonobligatory, at most, supportive role in the action of the catecholamines on cardiac contraction.
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PMID:Adenosine 3',5'-monophosphate, the myocardial cell membrane, and calcium. 17 10

1. Troponin I isolated from fresh cardiac muscle by affinity chromatography contains about 1.9 mol of covalently bound phosphate/mol. Similar preparations of white-skeletal-muscle troponin I contain about 0.5 mol of phosphate/mol. 2. A 3':5'-cyclic AMP-dependent protein kinase and a protein phosphatase are associated with troponin isolated from cardiac muscle. 3. Bovine cardiac 3':5'-cyclic AMP-dependent protein kinase catalyses the phosphorylation of cardiac troponin I 30 times faster than white-skeletal-muscle troponin I. 4. Troponin I is the only component of cardiac troponin phosphorylated at a significant rate by the endogenous or a bovine cardiac 3':5'-cyclic AMP-dependent protein kinase. 5. Phosphorylase kinase catalyses the phosphorylation of cardiac troponin I at similar or slightly faster rates than white-skeletal-muscle troponin I. 6. Troponin C inhibits the phosphorylation of cardiac and skeletal troponin I catalysed by phosphorylase kinase and the phosphorylation of white skeletal troponin I catalysed by 3':5'-cyclic AMP-dependent protein kinase; the phosphorylation of cardiac troponin I catalysed by the latter enzyme is not inhibited.
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PMID:The phosphorylation of troponin I from cardiac muscle. 17 90

Cholera toxin, an activator of adenylate cyclase in a wide variety of cells, is a substrate for the phosphotransferase reaction catalyzed by purified cyclic adenosine 5'-monophosphate dependent bovine cardiac muscle protein kinase and the protein associated with human erythrocyte membranes. Phosphorylation occurs when the toxin is dissociated with 5-20 mM dithiothreitol and is restricted to the A1 or "adenylate cyclase activating" subunit of the toxin.
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PMID:Phosphorylation of the active, A1 component of cholera toxin by protein kinase. 18 Oct 50

The adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase purified from bovine cardiac muscle catalyzes the transfer of up to 2 mol of 32P from [lambda-32P]ATP to seryl residues in its cyclic nucleotide-binding protein component (Erlichman, J., Rosenfeld, R., and Rosen, O. M. (1974) J. Biol. Chem. 249, 5000-5003). We now present three lines of evidence to support our conclusions that the undissociated holoenzyme does not catalyze the phosphorylation of exogenous substrates but can undergo self-phosphorylation by an intramolecular reaction: (a) addition of either cAMP-binding protein or the protein kinase inhibitor (Walsh, D. A., Ashby C. D., Gonzales, C., Calkins, D., Fischer, E. H., and Krebs, D. G. (1971) J. Biol. Chem. 241, 1977-1985) does not inhibit self-phosphorylation as it does phosphorylation of exogenous substrates in the presence or absence of cAMP; (b) addition of catalytic subunit to an excess of cyclic nucleotide-binding protein results in phosphorylation equivalent to the amount of holoenzyme so generated; (c) the rate of self-phosphorylation is not affected by dilution of the holoenzyme.
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PMID:Mechanism of self-phosphorylation of adenosine 3':5'-monophosphate-dependent protein kinase from bovine cardiac muscle. 18 91

A phosphoprotein phosphatase that catalyzes the dephosphorylation of cyclic adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase from bovine cardiac muscle has been purified to homogeneity by a modification of the procedure of Brandt et al. (Brandt, H., Capulong, Z.L., and Lee, E. Y. C. (1975) J. Biol. Chem. 250, 8038-8044). Treatment of the enzyme preparation with ethanol during the early stages of purification results in activation concomitant with reduction in molecular weight to 30,000. The purified activated enzyme has a Km for phospho-protein kinase in the presence or absence of 1.2 mM Mn2+ of 5 and 22 micronM, respectively. Phosphatase activity on phospho-protein kinase but not on other phosphoprotein substrates was cAMP-dependent. This selective activation by cAMP reflects the preference of the phosphatase for the free, phosphorylated cAMP-binding protein rather than the phosphoholoenzyme.
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PMID:Purification of phosphoprotein phosphatase from bovine cardiac muscle that catalyzes dephosphorylation of cyclic AMP-binding protein component of protein kinase. 19 23

The photoaffinity label 8-azido[32P]adenosine 3':5'-monophosphate (8-azido-cyclic [32P]AMP) was used to analyze both the cAMP-binding component of the purified cAMP-dependent protein kinase, and the cAMP-binding proteins present in crude tissue extracts of bovine cardiac muscle. 8-Azido-cyclic [32P]AMP reacted specifically and in stoichiometric amounts with the cAMP-binding proteins of bovine cardiac muscle. Upon phosphorylation, the purified cAMP-binding protein from bovine cardiac muscle changed its electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels from an apparent molecular weight of 54,000 to an apparent molecular weight of 56,000. In tissue extracts of bovine cardiac muscle, most of the 8-azido-cyclic [32P]AMP was incorporated into a protein band with an apparent molecular weight of 56,000 which shifted to 54,000 upon treatment with a phosphoprotein phosphatase. Thus a substantial amount of the cAMP-binding protein appeared to be in the phosphorylated form. Autoradiograms following sodium dodecyl sulfate-polyacrylamide gel electrophoresis of both the pure and impure cAMP-binding proteins labeled with 8-azido-cyclic [32P]AMP revealed another binding component with a molecular weight of 52,000 which incorporated 32P from [gamma-32P]ATP without changing its electrophoretic mobility. Limited proteolysis of the 56,000- and 52,000-dalton proteins labeled with 32P from either [gamma-32P]ATP.Mg2+ or 8-azido-cyclic [32P]AMP showed patterns indicating homology. On the other hand, peptide maps of the major 8-azido-cyclic [32P]AMP-labeled proteins from tissue extracts of bovine cardiac muscle (Mr = 56,000) and rabbit skeletal muscle (Mr = 48,000) displayed completely different patterns as expected for the cAMP-binding components of types II and I protein kinases. Both phospho- and dephospho-cAMP-binding components from the purified bovine cardiac muscle protein kinase were also resolved by isoelectric focusing on polyacrylamide slab gels containing 8 M urea. The phosphorylated forms labeled with 32P from either [gamma-32P]ATP or 8-azido-cyclic [32P]AMP migrated as a doublet with a pI of 5.35. The 8-azido-cyclic [32P]AMP-labeled dephosphorylated form also migrated as a doublet with a pI of 5.40. The phosphorylated and dephosphorylated cAMP-binding proteins migrated with molecular weights of 56,000 and 54,000, respectively, following a second dimension electrophoresis in sodium dodecyl sulfate. The lower molecular weight cAMP-binding component (Mr = 52,000) was also apparent in these gels. Similar experiments with the cAMP-binding proteins present in tissue extracts of bovine cardiac muscle indicate that they are predominantly in the phosphorylated form.
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PMID:Resolution of the phosphorylated and dephosphorylated cAMP-binding proteins of bovine cardiac muscle by affinity labeling and two-dimensional electrophoresis. 21 41


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