Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Giant fibres of the barnacle Balanus nubilus have been used as a preparation for studying the mode of action of cAMP on sodium transport. 2. It is shown that a concentration of cAMP as low as 10(-6)M, when micro-injected, causes a sharp rise in the radio-Na efflux. Ouabain fails to reverse the cAMP effect. 3. The magnitude of the response of the Na efflux to cAMP is markedly reduced by pre-injecting 100 or 500 mM-EGTA solutions or by omitting Ca2+ from the bathing medium. Both together fail to bring about a greater reduction in the response. 4. The response to cAMP is greatly reduced by pre-injecting the protein inhibitor of Walsh and practically abolished by pre-injecting 500 mM-EGTA and soaking in Ca-free artificial sea water, ASW. 5. The Ca2+-independent component of the Na efflux which is also stimulated by cAMP is shown to involve Na for H exchange. The magnitude of this exchange is governed by external pH. 6. The Na efflux into Ca2+-free, Li+-ASW is shown to be markedly stimulated by injecting cAMP, an effect which is enhanced by reducing external pH. 7. The Na efflux at 0 degrees C is stimulated by injecting cAMP. This is shown to be related to activation of the protein kinase by cAMP and to depend on the presence of external Ca2+. 8 (i) Ethacrynic acid when injected reduces the ouabain-insensitive Na efflux into HEPES-Ca2+-free ASW at pH 6-3. These same fibres show a marked response to cAMP. (II) The ouabain-insensitive Na efflux into HCO3-, Ca2+-free ASW from fibres pre-treated with ethacrynic acid fails to respond to external acidification. This is interpreted as indicating that ethacrynic acid inactivates the CO2-sensitive adenyl cyclase system. These same fibres when injected with cAMP show a marked response. (iii) Stimulation of the ouabain-insensitive Na efflux into HCO-3, Ca2+-free ASW by external acidification is reversed by injecting ethacrynic acid. These fibres when injected with cAMP show a reduced response. 9. It is concluded that: (i) stimulation of the Na efflux by injected cAMP is mainly due to activation of cAMP-dependent protein kinase; (ii) the underlying exchange mechanism consists of Na:Ca and Na:H exchange. Interaction of Ca2+ with a phosphorylated membrane, thereby modifying permeability remains as a real possibility; (iii) the site of action of CO2 and ethacrynic acid is the adenyl cyclase system. 10. The implications of activation of the adenyl cyclase system by CO2 and Na:H exchange are briefly touched upon.
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PMID:Mode of stimulation by adenosine 3':5'-cyclic monophosphate of the sodium efflux in barnacle muscle fibres. 18 61

A thermostable inhibition of ATP-protein phosphotransferase (EC 2.7.1.37) (protein kinase) which is present in crude tissue extracts has been resolved by gel chromatography (Sephadex G-100) into two molecular forms. These two forms will be referred to as type I and type II inhibitor. The type I inhibitor (Mr approximately or equal to 24,000) is specific for cAMP-dependent protein kinase and corresponds to the inhibitor described earlier (Walsh, D. A., Ashby, C. D., Gonzalez, C., Calkins, D., Fisher, E. H., and Krebs, E. G. (1971) J. Biol. Chem. 246, 1977-1985). The type II inhibitor (Mr approximately or equal to 15,000) competes for the enzyme with various substrate proteins (histone, alpha-casein, and Leu-Arg-Arg-Ala-Ser-Leu-Gly (kemptide). The type II inhibitor blocks protein phosphorylation catalyzed by several types of protein kinases (cAMP- and cGMP-dependent or cyclic nucleotide-independent protein kinases). The type II inhibitor from rat brain has been purified 1500-fold; this protein is thermostable, has acidic characteristics, and does not require Ca2+ ions for its activity. Different ratios and concentrations of type I and type II inhibitors of protein kinase are found in rat skeletal muscle, pancreas, cerebellum and corpus striatum, and in lobster tail muscle.
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PMID:Endogenous protein kinase inhibitors. Purification, characterization, and distribution in different tissues. 19 48

The effects of perfusate epinephrine, 1-methyl-3-isobutylxanthine, calcium, and filling pressure were investigated in the perfused working rat heart. Epinephrine produced a rapid increase in cAMP, in the protein kinase activity ratio, and in active phosphorylase. These effects preceded the increase in contractile force produced by the hormone. There was good correlation between protein kinase activation and the increase in force. Epinephrine and the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine were synergistic in their stimulatory effects on cAMP, protein kinase activity, active phosphorylase, and contractile force. When an increase in the force of contraction was produced either by increasing the filling pressure of the heart or by increasing the perfusate Ca2+ concentration, there was no change in either cAMP levels or protein kinase activity. These data suggest that the effect of beta-adrenergic catecholamines on contractile force is due, at least in part, to cAMP-dependent protein kinase activation. The increase in contractile force produced either by increasing the filling pressure (Frank-Starling phenomenon) or by increasing the perfusate Ca2+ concentration is apparently not mediated by cAMP or the protein kinase.
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PMID:Involvement of cAMP-dependent protein kinase in the regulation of heart contractile force. 19 11

Properties of the ATP-dependent calcium transport system of heart sarcolemma are presented. Calcium accumulation (with oxalate) in sarcolemma was increased due to cAMP-dependent protein kinase and phosphorylase b kinase. Protein kinase increased the Vmax of the sarcolemmal calcium accumulation without any detectable effect on the affinity for Ca2+. Both kinases failed to stimulate calcium binding. Protein kinase catalyzed phosphorylation of membrane proteins of molecular weights of 100,000, 25,000, and 14,000. Phosphorylase b kinase also catalyzed phosphorylation of these proteins. Protein kinase stimulated ATPase activity of sarcolemma. Sarcolemma contained endogenous protein kinase and protein phosphatase activities.
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PMID:Characteristics of heart sarcolemmal calcium transport system and effect of protein kinase on sarcolemmal calcium accumulation. 20 83

The heat-stable protein (protein kinase modulator), partially purified from fresh bovine heart, possessed the ability to inhibit and stimulate adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase and guanosine 3':5'-monophosphate (cGMP)-dependent protein kinase activities, respectively. The inhibitory activity of protein kinase modulator on cAMP-dependent protein kinase was abolished almost completely by trypsin treatment, while the ability to stimulate cGMP-dependent protein kinase activity was resistant to trypsin. Fractionation by a linear potassium phosphate gradient on DEAE-cellulose column did not clearly separate both activities. Phosphorylation of cardiac microsomal component, "phospholamban" (molecular weight = 22,000), was inhibited almost completely by the saturating amounts of protein kinase modulator. This inhibition of phospholamban phosphorylation by protein kinase modulator was accompanied by a decreased Ca uptake rate that had been stimulated by cAMP-dependent protein kinase. These findings indicate that protein kinase modulator is functional in controlling the cAMP-dependent protein kinase-catalyzed phosphorylation of phospholamban and the rate of calcium transport, lending further support for the previously proposed mechanism, in which phospholamban is assumed to serve as a regulator of calcium transport in cardiac sarcoplasmic reticulum.
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PMID:Effect of protein kinase modulator on cAMP-dependent protein kinase-catalyzed phosphorylation of phospholamban and stimulation of calcium transport in cardiac sarcoplasmic reticulum. 20 86

Similar time courses were obtained for decreases in the rate of calcium transport by cardiac sarcoplasmic reticulum vesicles previously phosphorylated by cAMP-dependent protein kinase and dephosphorylation of the 22,000-dalton phosphoprotein in these membranes. Dephosphorylation of the 22,000-dalton phosphoprotein can be attributed to a phosphoprotein phosphatase in the sarcoplasmic reticular membranes. This membrane-bound phosphoprotein phosphatase may play a role in the reversal of the relaxation-promoting effect of catecholamines on the heart.
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PMID:Phosphoprotein phosphatase-catalyzed dephosphorylation of the 22,000-dalton phosphoprotein of cardiac sarcoplasmic reticulum. 20 87

A protein kinase which depends on the simultaneous presence of Ca2+ and the modulator protein for its histone phosphorylation activity has been demonstrated in rabbit skeletal muscle and partially purified. The purified enzyme was not activated by cAMP, cGMP, or incubation with trypsin. Nor was the enzyme inhibited by the protein inhibitor of cAMP-dependent protein kinase. In addition to histone, myosin light chains and phosphorylase kinase served as substrates for the protein kinase, and their phosphorylation also depended on the presence of Ca2+ and the modulator protein. The phosphorylation of phosphorylase kinase was accompanied with a marked activation of the enzyme. The results suggest that the protein kinase has multiple functions and may be involved in the mediation of Ca2+ effects in many biological processes. It is proposed that this enzyme be designated as the modulator-dependent protein kinase. The modulator-dependent protein kinase may be identical to the myosin light chain kinase; chicken gizzard light chain kinase has been shown activatable by the modulator protein (Dabrowska, R., Sherry, J. M. F., Aramatorio, D. K., and Hartshorne, D. J. (1978) Biochemistry 17, 253-258).
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PMID:The modulator-dependent protein kinase. A multifunctional protein kinase activatable by the Ca2+-dependent modulator protein of the cyclic nucleotide system. 20 40

Epinephrine rapidly activates phosphorylase in hepatocytes, mainly by a mechanism(s) involving alpha-adrenergic and not beta-adrenergic receptors. The alpha-adrenergic mechanism does not involve accumulation of cAMP or activation of cAMP-dependent protein kinase. It is impaired when hepatocytes are depleted of calcium by EGTA treatment and is rapidly restored by readdition of calcium. Basal phosphorylase is also lowered by calcium deficiency and rapidly increased by calcium but not other divalent cations. The divalent cation ioniphore A23187 increases phosphorylase a levels in hepatocytes in a calcium-dependent manner. Calcium deficiency does not modify the effects of glucagon, cAMP, or beta-adrenergic activation on phosphorylase. Activation of alpha-adrenergic receptors rapidly increases 45Ca fluxes in hepatocytes. Glucagon produces similar effects, but supraphysiological concentrations are required. The hypothesis is advanced that alpha-adrenergic activation of phosphorylase involves alterations in cell calcium such that there is an increase in cytosolic Ca2+ concentration leading to increased phosphorylase kinase activity. Epinephrine induces greater cAMP accumulation in calcium-depleted cells than in normal cells. The effect is mediated by alpha-adrenergic and not beta-adrenergic receptors. Calcium deficiency also cuases cAMP accumulation in hepatocytes incubated with phenylephrine but does not modify the responses of the cells to isoproterenol, glucagon, or cAMP. Low concentrations of calcium rapidly reverse alpha-adrenergic receptor-mediated cAMP accumulation in calcium-depleted cells. The hypothesis is advanced that calcium normally exerts an inhibitory effect on a linkage between alpha-adrenergic receptors and adenylate cyclase in hepatocytes.
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PMID:Mechanisms of catecholamine actions on liver carbohydrate metabolism. 20 89

The recently discovered heat-stable inhibitor protein of the Ca2+-activated cyclic nucleotide phosphodiesterase (Sharma, R. K., Wirch, E. & Warg, J. H. (1978) J. Biol. Chem., in press) has been purified 238 214-fold from bovine brain extract using an affinity column of the modulator protein--Sepharose 4B conjugate. The purified sample appears to be homogeneous as judged by sodium dodecyl sulphate (SDS) gel electrophoresis. The protein band has a mobility corresponding to that of a polypeptide of molecular weight 68 000. Since the heat-stable inhibitor protein has a molecular weight of 70 000 under nondenaturing conditions, it suggests that it is a monomeric protein. The protein has no inhibitory activity toward the cAMP-dependent protein kinase or protein phosphatase. The purified sample has been tested for various enzyme activities which include ATPase, GTPase, cAMP phosphodiesterase, cGMP phosphodiesterase, 5'-nucleotidase, and protein kinase. None of these activities are exhibited by the purified sample.
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PMID:Purification of the heat-stable inhibitor protein of the Ca2+-activated cyclic nucleotide phosphodiesterase by affinity chromatography. 20 31

This study was initiated in order to elaborate further on the mechanism by which epinephrine modulates cardiac function via protein phosphorylation. A membrane fraction has been isolated from freeze-clamped perfused rat heart that contains two phosphoproteins. These proteins have molecular weights of 36,000 (A protein) and 27,000 (B protein). The phosphorylation of the A protein occurs during the equilibration of the heart with inorganic [32P]phosphate. The phosphorylation of the B protein occurs in response to epinephrine. The A and B proteins are apparently identical with two phosphoproteins in enriched preparations of sarcolemma. The protein of the sarcolemma preparation equivalent to the A protein is phosphorylated in vitro by both cAMP-independent and cAMP-dependent protein kinases. The phosphorylation of the protein of the sarcolemma preparation equivalent to the B protein is catalyzed by the cAMP-dependent protein kinase. Thus the patterns of phosphorylation of these proteins in vivo and in vitro are compatible. The phosphorylation of the B protein has been documented in vitro to modulate calcium transport (Will, H., et al. (1973) Acta Biol. Med. Ger. 31, 45-52), but the response to epinephrine in the perfused heart is not apparently coordinated with the catecholamine-induced inotropic effect.
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PMID:Cyclic adenosine monophosphate dependent and independent phosphorylation of sarcolemma membrane proteins in perfused rat heart. 21 27


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