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)

The effect of the Ca2+-calmodulin antagonist trifluoperazine on the elevation of phosphorylation of rat liver small ribosomal subunit protein S6 induced by the hepatotoxic agent D-galactosamine has been studied. Trifluoperazine applied in various doses (1-100 mg/kg body wt) before injection of D-galactosamine into the rat does not reverse the strong increase in phosphorylation promoted by D-galactosamine. Instead, trifluoperazine has been identified as a potent stimulator of S6 phosphorylation in normal rat liver in vivo without causing significant changes in the cyclic AMP content of liver and the overall rate of liver protein synthesis. Both drugs, however, were not effective in stimulating the incorporation of [32P]phosphate into microsomes or crude ribosomes in liver slices in vitro. The results suggest that a calmodulin-activated protein kinase probably is not primarily engaged in S6 phosphorylation produced by D-galactosamine. However, further in vitro studies are needed to reach a definite conclusion.
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PMID:The effect of trifluoperazine on the phosphorylation of ribosomal small subunit protein S6 in D-galactosamine-injured and normal rat liver. 630 3

A new species of protein kinase has been identified in cytosol preparations from bovine corpora lutea. Enzyme activity required the simultaneous presence of Ca2+ and phospholipid, and was also enhanced by glyceryl dioleate. Phosphatidylserine was the most effective phospholipid for stimulating histone phosphorylation. Other phospholipids capable of supporting enzymic activity were, in order of decreasing activity, phosphatidylinositol, phosphatidic acid, cardiolipin and phosphatidylglycerol. Several other phospholipids tested were ineffective. A cyclic AMP-dependent protein kinase was also present in the luteal cytosol. This enzyme activity was eliminated by protein kinase inhibitor without affecting the Ca2+- and phospholipid-stimulated activity. Lysine-rich histone (IIIS) was a much better substrate than type-IIA histone for Ca2+- and phospholipid-dependent phosphorylation. Ca2+ and phospholipid also enhanced phosphorylation of endogenous luteal cytosol protein. Calmodulin, alone or in the presence of Ca2+, was unable to increase phosphorylation. Trifluoperazine inhibited protein kinase activity stimulated by Ca2+ and phospholipid. These data suggest that a phospholipid-sensitive, Ca2+-dependent protein kinase may provide an important link between hormonally-induced changes in phospholipid metabolism and corpus-luteum function.
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PMID:Activation of protein kinase in the bovine corpus luteum by phospholipid and Ca2+. 631 Nov 89

As in other cells, cAMP-dependent (protein kinase A) and calcium-dependent protein kinases are present in the rabbit peritoneal neutrophil. The major substrates for protein kinase A in the cytosol of rabbit peritoneal neutrophil is a 43 kDa protein which appears to be actin (pI 5.7). The other substrates for protein kinase A in the cytosol are very acidic proteins with molecular weights of 135000 (pI 4.6) and 130 000 (pI 4.8). Two classes of calcium-dependent protein kinases are present in the rabbit peritoneal neutrophil: one is calcium, calmodulin-dependent, the other is calcium, phosphatidylserine-dependent. Phosphatidylserine appears to be much more effective than calmodulin in stimulating calcium-dependent protein kinase activity. The phospholipid-sensitive, calcium-dependent protein kinase (protein kinase C), present only in the cytosol fraction, exhibits much higher activity than the cAMP-dependent protein kinase from the same source. At least four substrates (Mr 130 000 (pI 4.6) 43 000 (pI 4.8), 41 000 (pI 6.3) and 34 000) of the protein kinase C in the cytosol were identified. Trifluoperazine, a compound which inhibits the degranulation, aggregation and stimulated oxygen consumption of rabbit peritoneal neutrophils. (Alobaidi, T., Naccache, P.H. and Sha'afi, R.I. (1981) Biochim. Biophys. Acta 675, 316-321), also inhibits the activity of protein kinase C. The possible role of cAMP-dependent and calcium-dependent phosphorylation system in neutrophil function is discussed.
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PMID:Endogenous substrates for cyclic AMP-dependent and calcium-dependent protein phosphorylation in rabbit peritoneal neutrophils. 631 Dec 79

The effects of alpha- and beta-adrenergic stimulation on ketogenesis were examined in freshly isolated rat hepatocytes in order to determine which alpha- or beta-adrenergic stimulation is involved in the enhancement of ketogenesis. In the presence of 0.3 mmol/L (U-14C)-palmitate, epinephrine, norepinephrine, and phenylephrine at 500 ng/mL increased ketogenesis by 25% (16.0 +/- 0.17 v 12.8 +/- 0.13 nmol/mg protein per hour), 20% (15.3 +/- 0.28) and 20% (15.4 +/- 0.36), respectively. However, isoproterenol even at 1 microgram/mL did not stimulate ketogenesis. Phentolamine (5 micrograms/mL) almost completely abolished the effect of epinephrine on ketogenesis (13.7 +/- 0.30 v 16.0 +/- 0.17) but propranolol did not inhibit the stimulation by epinephrine (15.6 +/- 0.38 v 16.0 +/- 0.17). Trifluoperazine (10 mumol/L), presumably an inhibitor of calcium-dependent protein kinase, abolished the effect of epinephrine (13.6 +/- 0.22 v 16.0 +/- 0.17). These results indicate that catecholamines increase ketogenesis predominantly through the alpha-adrenergic system independent of cyclic AMP, and calcium-dependent protein kinase is thought to be involved in the activation of ketogenesis. On the other hand, glucagon stimulated ketogenesis with an increase of cyclic AMP, which was not inhibited by alpha- and beta-adrenergic antagonists. Alpha-adrenergic stimulation increased hepatic glycogenolysis much more at much lower concentrations when compared with ketogenesis. Stimulation of ketogenesis by catecholamines seemed to be less sensitive and responsive compared with hepatic glycogenolysis.
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PMID:Mechanism of adrenergic stimulation of hepatic ketogenesis. 635 38

The characteristics of contraction and relaxation of membrane skinned smooth muscle from guinea pig trachealis muscle are described. Micromolar Ca2+ elicited reproducible contractions in Mg-ATP salt solution at 20 degrees C. The speed of contraction was much faster at 30 and 37 degrees C, enabling cumulative concentration-response curves to be obtained. At these temperatures, a progressive increase in basal tension occurred in the absence of Ca2+. This tension was active and developed more rapidly at pH 6.7 than at pH 7.0. Calmodulin (0.1-10 microM) greatly increased the speed of contraction and lowered the threshold Ca2+ concentration ([Ca2+]) required to initiate contraction from 0.13 to 0.02 microM Ca2+. Trifluoperazine antagonized responses to Ca2+. Thiophosphorylation with adenosine 5'-O-(3-thiotriphosphate) produced maximum tension development, which was Ca2+-independent. This effect was reversible. The results are compatible with myosin-linked regulation of contraction in which a Ca2+ X calmodulin complex activates myosin light chain kinase to phosphorylate myosin. The catalytic subunit of cAMP-dependent protein kinase strongly inhibited tension development and slowly relaxed fibers contracted with threshold [Ca2+] consistent with an action via phosphorylation of myosin light chain kinase. This effect was extremely slow compared with the rate of relaxation by Ca2+ withdrawal or with relaxation of intact smooth muscle by beta-adrenergic agonists.
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PMID:Effect of calmodulin, Ca2+, and cAMP protein kinase on skinned tracheal smooth muscle. 670 44

Calmodulin and Ca2+- and calmodulin-dependent protein kinase were identified in the rat anterior pituitary gland. The concentration of calmodulin was 1.18 +/- 0.11 microgram/mg protein (n = 7) in the cytosol fraction. The calmodulin of the anterior pituitary gland co-migrated with brain calmodulin on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The Ka value of the partially purified enzyme for Ca2+ was 3.3 microM in the presence of 0.30 microM calmodulin. Trifluoperazine and chlorpromazine, calmodulin-interacting agents, inhibited enzyme activity, with Ki values of 1.3 and 2.6 X 10(-5) M, respectively. The enzyme was resolved into two peaks of activity, with sedimentation coefficients of 5.5 S and 16.5 S, by sucrose density gradient centrifugation. At least nine proteins were phosphorylated by the enzyme in a Ca2+- and calmodulin-dependent manner. In light of these results, the possibility that calmodulin and the calmodulin-activatable protein kinase system are involved in the mediation of the Ca2+ effect on hormone release from the anterior pituitary gland must be given consideration.
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PMID:Calmodulin and Ca2+- and calmodulin-dependent protein kinase in rat anterior pituitary gland. 683 39

Recent evidence suggests that a melatonin (MEL) mechanism of action may be through modulation of Ca2+-activated calmodulin (CaM). MEL binds to CaM with a high affinity, and has been shown to act as a CaM antagonist. Among the CaM-dependent enzymes, Ca2+/Calmodulin-dependent protein kinase II (CaM-kinase II) is a particularly abundant enzyme in the nervous system. In the brain it phosphorylates a broad spectrum of substrates, thus modulating important neuronal functions. We describe the MEL effect on CaM-kinase II activity in vitro. CaM-kinase II was purified from rat brain by column chromatography, and identified by Western immunoblotting. CaM-kinase II activity was assessed in the presence of Ca2+/CaM by the kinase's ability to phosphorylate the synthetic substrate syntide-2 and by enzyme autophosphorylation. MEL inhibited CaM-kinase II activity, and enzyme autophosphorylation. Inhibition of the enzyme by 10(-9) M MEL was nearly of 30%. Trifluoperazine (10 microM), W7 (10 microM), and compound 48/80 (30 micrograms/ml), inhibited CaM-kinase II activity by 40%, 42%, and 93%, respectively. Both EGTA (5 mM) and MEL (10(-5) M) abolished autophosphorylation. The effect of MEL on CaM-kinase II activity was specific, since neither serotonin, N-acetylserotonin, nor 6-hydroxymelatonin inhibited its activity. Our results support the hypothesis that MEL acts as a CaM antagonist and cellular functions may be rhythmically regulated by MEL modulation of CaM-dependent protein phosphorylation.
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PMID:In vitro inhibition of Ca2+/calmodulin-dependent kinase II activity by melatonin. 864 23

Ca2+/calmodulin- and cAMP-dependent protein kinase activities were characterized in two subcellular membrane samples. Membranes from rat lacrimal gland were isolated by differential and density gradient centrifugation into six density windows. The present study focused on membranes from density windows III and V which contain mixtures of apical, Golgi, endosomal, and endoplasmic reticulum membranes in different proportions. Phosphorylation of membrane proteins was measured by incubating the samples in [g-32P]ATP and separating the proteins by discontinuous SDS-PAGE followed by autoradiography. The amount of phosphate incorporated into specific peptide bands was quantified by densitometry. Ca2+/calmodulin-dependent protein kinase phosphorylated a 52,000 MW peptide in membranes from both density windows with a maximal increase from 0.3 to 66 microM free Ca2+. Trifluoperazine and promethazine, two inhibitors of Ca2+/calmodulin-dependent protein kinases, inhibited this phosphorylation. cAMP-dependent protein kinase phosphorylated a 22,000 MW peptide and a 91,000 MW peptide which were present in membranes from density window III only. We conclude that a Ca2+/calmodulin-dependent protein kinase activity is present in membranes from both density window III and V whereas a cAMP-dependent protein kinase activity is present only in membranes from density window III.
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PMID:Protein phosphorylation in Golgi, endosomal, and endoplasmic reticulum membrane fractions of lacrimal gland. 867 Jul 24


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