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)

C-protein, a thick filament-associated protein, has been isolated from bovine myocardium and found to be a substrate in vitro of the Ca2+- and phospholipid-dependent protein kinase (protein kinase C). Incorporation of approximately 1.6 mol Pi/mol C-protein was observed. This phosphorylation was dependent on both Ca2+ and a phospholipid (L-alpha-phosphatidyl-L-serine was used). Phosphate incorporation specifically into C-protein was verified by SDS-polyacrylamide gel electrophoresis and autoradiography and was almost exclusively into serine residues (86.9%), with only a small amount of phosphothreonine (13.1%) and no phosphotyrosine being detected. Two-dimensional thin-layer electrophoresis of a chymotryptic digest of phosphorylated C-protein indicated site specificity of phosphorylation. Cardiac C-protein is known to be a substrate of cAMP-dependent protein kinase both in vitro and in vivo (Jeacocke, S.A. and England, P.J. (1980) FEBS Lett. 122, 129-132). Isolated bovine cardiac C-protein was rapidly phosphorylated, to the extent of 5 mol/mol, by the purified catalytic subunit of cAMP-dependent protein kinase. Phosphorylation catalyzed by these two protein kinases was not additive, suggesting that the sites phosphorylated by protein kinase C are also phosphorylated by cAMP-dependent protein kinase. Chicken cardiac muscle has also been shown to contain a Ca2+, calmodulin-dependent protein kinase which phosphorylates C-protein (Hartzell, H.C. and Glass, D.B. (1984) J. Biol. Chem. 259, 15587-15596). The physiological role of cardiac C-protein may therefore be subject to regulation by multiple protein kinases.
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PMID:Phosphorylation of bovine cardiac C-protein by protein kinase C. 384 Sep 98

Chemically skinned (Lubrol WX) cardiac muscle fibers produce half-maximum isometric tension at pCa 6.18 (pH 6.7) in presence of MgATP (10 mM). After addition of cGMP (5 microM) and cGMP-dependent protein kinase (0.1 microM), the pCa required for half-maximum activation is 5.96, while maximum tension is not affected. Similar shifts in the tension/pCa-relationship have been observed after incubation of skinned cardiac muscle fibers with cAMP of catalytic subunit of the cAMP-dependent protein kinase. The shift in the Ca2+-sensitivity is associated with an increased incorporation of radioactivity into a Mr 28000 band (presumably troponin-I) and a Mr 145000 band.
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PMID:cGMP-dependent protein kinase decreases calcium sensitivity of skinned cardiac fibers. 618 64

In detergent-treated cardiac muscle fibers, forskolin, a potent activator of adenylate cyclases, inhibits tension development elicited with submaximal [Ca2+] and increases incorporation of 32P into troponin-I. A similar reduced tension development has been observed after treatment with cAMP or the catalytic subunit of the cAMP-dependent protein kinase. It is concluded that these fibers still contain much of the enzyme cascade involved in evoking a contractile response to beta-adrenergic stimulation.
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PMID:Forskolin inhibits tension development in detergent-treated cardiac muscle fibers. 619 1

A unique set of high molecular weight proteins was identified in junctional sarcoplasmic reticulum (SR) vesicles isolated from both cardiac muscle and skeletal muscle. These high Mr proteins were not present in free SR vesicles isolated from either tissue, nor were they observed in purified sarcolemmal fractions. The junctional SR high Mr proteins migrated as doublets in sodium dodecyl sulfate-polyacrylamide gels and exhibited apparent Mr values between 290,000 and 350,000. The high Mr proteins bound calmodulin; they were the principal proteins labeled in the cardiac and skeletal muscle SR subfractions by azido-125I-calmodulin. The high Mr proteins were also substrates for an endogenous Ca2+-calmodulin-dependent protein kinase activity, as well as exogenously added catalytic subunit of cAMP-dependent protein kinase. In addition, the junctional SR high Mr proteins were the major SR proteins degraded by a Ca2+-activated protease purified from smooth muscle. Control experiments verified the separation of junctional SR vesicles and free SR vesicles from both muscle types. Junctional SR vesicles were enriched in calsequestrin, and they exhibited Ca2+ uptake which was stimulated up to 10-fold by either ryanodine or ruthenium red. Free SR vesicles were deficient in calsequestrin and were insensitive to these two agents. Localization of the cardiac and skeletal muscle high Mr proteins to the junctional SR, coupled with demonstration of their nearly identical biochemical properties, suggests that the proteins are homologous and are likely to have similar functions in both types of striated muscle.
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PMID:High molecular weight proteins in cardiac and skeletal muscle junctional sarcoplasmic reticulum vesicles bind calmodulin, are phosphorylated, and are degraded by Ca2+-activated protease. 620 12

1. Hybrid or reconstituted troponins were prepared from troponin components of rabbit skeletal muscle and porcine cardiac muscle and their effect on the actomyosin ATPase activity was measured at various concentrations of Ca2+ or Sr2+. The Ca2+ concentration required for half-maximum activation of actomyosin ATPase with troponin containing cardiac troponin I was slightly higher than that with troponin containing skeletal troponin I. The Sr2+ concentration required for half-maximum activation of actomyosin ATPase with troponin containing skeletal troponin C was higher than that with troponin containing cardiac troponin C. 2. Reconstituted cardiac troponin was phosphorylated by cyclic AMP-dependent protein kinase. The Ca2+ sensitivity of actomyosin ATPase with cardiac troponin decreased upon phosphorylation of troponin I; maximum ATPase activity was depressed and the Ca2+ concentration at half-maximum activation increased. On the other hand, phosphorylation of troponin I did not change Sr2+ sensitivity. 3. The inhibitory effect of cardiac troponin I on the actomyosin ATPase activity was neutralized by increasing the amount of brain calmodulin at high Ca2+ and Sr2+ concentrations but not at low concentrations. 4. ATPase activity of actomyosin with a mixture of troponin I and calmodulin was assayed at various concentrations of Ca2+ or Sr2+. The Ca2+ or Sr2+ sensitivity of actomyosin ATPase containing skeletal troponin I was approximately the same as that of actomyosin ATPase containing cardiac troponin I. Phosphorylation of cardiac troponin I did not change the Ca2+ sensitivity of the ATPase. 5. The Ca2+ or Sr2+ concentration required for half-maximum activation of actomyosin ATPase with troponin I-T-calmodulin was higher than that of actomyosin ATPase with the mixture of troponin I and calmodulin. Maximum ATPase activity was lower than that with the mixture of troponin I and calmodulin.
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PMID:Sensitivity of actomyosin ATPase to calcium and strontium ions. Effect of hybrid troponins. 622 22

1. The relaxing action of the beta-adrenergic agent, isoprenaline, on the porcine coronary artery was investigated in relation to the cyclic AMP level, the endogenous binding of cyclic AMP to the regulatory unit of cyclic AMP dependent protein kinase or the phosphorylation as a result of activation of protein kinase of the muscle homogenate in Krebs solution and excess [K]o solution. These relations were also compared with those of the rat cardiac muscle, in which isoprenaline showed a positive inotropic action. 2. Excess [K]o decreased the cyclic AMP level in proportion to the amplitude of K-induced contracture in the porcine coronary artery. Isoprenaline increased the cyclic AMP level in Krebs solution, while it had no effect in excess [K]o. 3. In the porcine coronary artery, the particulate fraction possessed only 5% of the total cyclic AMP dependent protein kinase, while in the rat cardiac muscle, the particulate fraction was 25% of the total protein kinase. 4. The cyclic AMP dependent protein kinase in the particulate fraction of the porcine coronary artery was already saturated with the endogenous cyclic AMP. However, the binding of cyclic AMP to the protein kinase in the particulate fraction in the cardiac muscle and in the cytosol fraction of both tissues were increased in accordance with the cyclic AMP level. In the coronary artery, the protein kinase in the cytosol fraction was bound to a greater extent with cyclic AMP than was measured in the rat cardiac muscle. 5. In the rat cardiac muscle, isoprenaline enhanced the phosphorylation, detected by autoradiography of SDS gel electrophoresis in individual fractions of phosphorylated protein, while little enhancement was observed in the porcine coronary artery. 6. These observations led to the conclusion that in the porcine coronary artery, beta-adrenergic agent increases the levels of cyclic AMP but does not increase the phosphorylation. If the phosphorylation catalysed by cyclic AMP dependent protein kinase was utilized for Ca mobilization in the cell, the change in the cyclic AMP level would probably not have a causal relation to the muscle tone. This conclusion, however, may not be applicable in the case of the cardiac muscle.
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PMID:Does activation of cyclic AMP dependent phosphorylation induced by beta-adrenergic agent control the tone of vascular muscle? 625 32

The complete amino acid sequence of the 349-residue catalytic subunit of cyclic AMP-dependent protein kinase from bovine cardiac muscle is presented. The sequence of the subunit (Mr 40,580 including phosphate groups at threonine-196 and serine-337) was derived largely by automated Edman degradation of nine fragments generated from the carboxymethylated protein by cleavage of methionyl bonds with cyanogen bromide. These fragments were aligned along the polypeptide chain by analysis of methionine-containing tryptic peptides isolated from protein radiolabeled in vitro by [14C]methyl exchange at methionyl residues. The molecule contains only two cysteinyl residues, at positions 198 and 342. It is relatively polar, containing clusters of cationic residues toward the amino terminus and anionic residues towards the carboxyl terminus. Predictions of secondary structure suggest the presence of three major domains with approximately half of the residues occurring in alpha-helices and 12% in beta-strands.
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PMID:Complete amino acid sequence of the catalytic subunit of bovine cardiac muscle cyclic AMP-dependent protein kinase. 626 77

The purpose of this investigation was to examine the effects of beta-adrenergic and muscarinic cholinergic agonists on protein phosphorylation in intact frog atrium. beta-Adrenergic agonists increase and muscarinic agonists decrease 32P incorporation into a 165,000-dalton (165K) protein within less than 1 min. The concentrations of isoproterenol that produce increases in 32P incorporation into the 165K protein and in systolic tension are similar. Further, the changes in 32P incorporation and tension produced by isoproterenol occur with similar time courses. Carbamylcholine decreases tension somewhat more quickly and at lower concentrations than it decreases 32P incorporation, however. Isoproterenol-stimulated 32P incorporation is thought to be mediated by cAMP-dependent protein kinase because bath application of dibutyryl cAMP, cholera toxin, or phosphodiesterase inhibitors increase 32P incorporation into the 165K protein in intact atria. When heart homogenates are incubated in the presence of [gamma-32P]ATP, cAMP stimulates the incorporation of 32P into the 165K protein. cGMP is much less effective. We suggest that carbamylcholine decreases 32P incorporation into the 165K protein by a mechanism independent of cAMP levels because carbamylcholine inhibits the stimulation of 32P incorporation into the 165K band produced by 8-bromo cAMP in intact cells. Phosphorylation of the 165K protein occurs in cardiac muscle but not in other tissues. We hypothesize that the 165K protein is C-protein, because the 165K- and C-proteins have similar solubilities and are associated with the myofibril. Further, antibodies produced against the 165K protein bind to C-protein purified from rabbit heart and also bind to the same region of the myofibril where C-protein is found.
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PMID:Effects of cholinergic and adrenergic agonists on phosphorylation of a 165,000-dalton myofibrillar protein in intact cardiac muscle. 627 7

The complete amino acid sequence of the regulatory subunit of type II cAMP-dependent protein kinase from bovine cardiac muscle is presented. Primary fragments for the sequence determination were obtained by limited proteolysis with various proteases or by cleavage with cyanogen bromide. The sequence of the 400 amino acid residues has two homologous regions, strongly suggesting tandem gene duplication. The predicted secondary structure suggests the presence of 42% alpha-helix, 23% beta-strand, and 23 beta-turns. The molecular weight of the subunit, as derived from the sequence, is 45,084 including a phosphate group at residue 95. This is significantly less than earlier estimates based on NaDodSO4 gel electrophoresis and sedimentation experiments. The structure is discussed in terms of putative sites of interaction with cAMP and with the catalytic subunit.
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PMID:Primary structure of the regulatory subunit of type II cAMP-dependent protein kinase from bovine cardiac muscle. 628 32

beta-Adrenergic stimulation of the heart is thought to increase cardiac muscle contractility by activation of cyclic AMP-dependent protein kinase and concomitant increase in the phosphorylation of certain proteins (for refs see refs 1-6). Electrophysiological studies have shown that the stimulation of cardiac beta-adrenoreceptors, the external application of cyclic AMP or its analogues to Purkinje fibres, or the injection of cyclic AMP into single myocytes can increase the slow inward current (Isi) during the plateau phase of the action potential (AP). In heart muscle this current is mainly carried by Ca2+ (refs 10, 11) and it has been suggested that cyclic AMP-dependent phosphorylation of some component of the calcium channel increases the amount of Ca2+ which enters the cell during depolarization. We have investigated this hypothesis by examining the electrical responses of isolated guinea pig ventricular myocytes to pressure injections of subunits of the cyclic AMP-dependent protein kinase. We report here that injection of the catalytic subunit (C) resulted in a lengthening of the action potential duration (APD) and an increase in the height of the plateau as well as the amplitude of Isi. By contrast, the injection of regulatory subunit (R) shortened the APD of fast and slow response APs, an effect which was reversed by adrenaline.
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PMID:Injection of subunits of cyclic AMP-dependent protein kinase into cardiac myocytes modulates Ca2+ current. 628 99


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