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)

The three major nuclear DNA-dependent RNA polymerases (enzymes I, II and III) were present in nuclear extracts from transplantable R-35 rat mammary tumors. Except for somewhat less enzyme III, their relative distribution resembled that of nuclear extracts from late-pregnant rats. When enzyme II from normal tissue extracts was incubated for RNA synthesis with cyclic AMP, inhibition was frequently observed, but this occurred less often with nuclear extracts from the R-35 tumor. In some experiments with both normal and tumor tissue, cyclic AMP and cyclic GMP increased the apparent activity of nucleolar enzyme Ib and nucleoplasmic enzyme II, respectively. Nuclear extracts from both normal and tumor tissue contain proteins which bind radioactive cyclic AMP and cyclic GMP. Their patterns of binding were not identical. These results are consistent with the following hypothesis: altered binding by the tumor of cyclic nucleotides to putative nuclear 'r-gulatory' proteins (e.g. protein kinase subunits, or possibly other high affinity cyclic nucleotide-binding proteins unrelated to protein kinases) contributes to atative nuclear 'regularory' proteins (e.g. protein kinase subunits, or possibly other high affinity cyclic nucleotide-binding proteins unrelated to protein kinases) contributes to and may be responsible for some of the differences in response to cyclic nucleotides that were observed. It is possible that such defects occur in other tumors, or even represent a fundamental defect in all cancer cells. Several explanations for these results are discussed.
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PMID:Solubilized nuclear DNA-dependent RNA polymerases from normal rat mammary glands and from transplantable R-35 rat mammary tumors. 17 42

Guanosine 3':5'-monophosphate (cyclic GMP)-dependent protein kinase (protein kinase G) partially purified from silkworm pupae was selectively activated by cyclic GMP at lower concentrations. Nevertheless, the enzyme seemed to differ from adenosine 3':5'-monophosphate-dependent protein kinase (protein kinase A) with respect to the mode of response to cyclic nucleotides. The catalytic activity and cyclic GMP-binding activity were not dissociated by cyclic GMP in a manner similar to that described for protein kinase A. The enzyme was not inhibited by regulatory subunit of protein kinase A nor by protein inhibitor. A sulfhydryl compound such as 2-mercaptoethanol or glutathione was essential for the activation by cyclic GMP, and an extraordinary high concentration of either Mg2+ (100 mM) or Mn2+ (25 mM) was needed for maximal stimulation by cyclic GMP. A polyamine such as spermine, spermidine, or putrescine could substitute partly for the cation. Kinetic analysis indicated that Km for ATP was decreased whereas Ka for cyclic GMP was increased significantly at high concentrations of the cation. The effect of the cation to decrease Km for ATP was not evident in the absence of a sulfhydryl compound. These characteristics of protein kinase G described above were not observed for protein kinase A which was obtained from the same organism.
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PMID:Comparison of mode of activation of guanosine 3':5'-monophosphate-dependent and adenosine 3':5'-monophosphate-dependent protein kinases from silkworm. 17 53

Guanosine 3':5'-monophosphate (cyclic GMP)-dependent protein kinase was purified from the guinea pig fetal lung, a tissue shown to be the richest in this enzyme in all mammalian sources examined, and its general properties studied. The enzyme was purified 150-fold from crude extract by steps of pH 5.4 isoelectric precipitation, Sephadex G-200 filtration, hydroxylapatite treatment and DEAE-cellulose chromatography. The purified enzyme, free from contamination with adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase, had a specific activity at least equivalent to 600-fold purification of the enzyme from the adult lung. The pulmonary enzyme exhibited an absolute requirement of protein kinase modulator (prepared from various mammalian tissues with an exception of skeletal muscle) for its activity. Inhibitor protein of cyclic AMP-dependent protein kinase purified from rabbit skeletal muscle could not stimulate nor inhibit the cyclic GMP target enzyme, indicating the factors from mammalian sources regulating the two classes of protein kinases may not be the same. The enzyme had Ka values of 1.3 times 10(-8) and 3.3 times 10(-8) M for 8-bromo cyclic GMP and cyclic GMP, respectively, compared to 3.0 times 10(-6) M for cyclic AMP. Cyclic GMP lowered the Km of the enzyme for ATP from 6.3 times 10(-5) M in its absence to 2.1 times 10(-5) M in its presence, accompanied by an approximate doubling of the Vmax. The molecular weight of the enzyme (assayed by its catalytic and cyclic GMP-binding abilities) was estimated to be 123,000, corresponding to a sedimendation coefficient of 7.06 S, by means of sucrose density gradient ultracentrifugation. The cyclic GMP-dependent enzyme required Mg2+ and Co2+ for its activity with optimal concentrations of about 30 and 0.7 mM, respectively. The maximal activity seen in the presence of Mg2+, however, was nearly twice as high as that seen in the presence of Co2+. Histones were generally effective substrates for the enzyme, whereas protamine, casein, phosvitin, phosphorylase kinase, and activator protein of phosphodiesterase were not. The cyclic GMP-dependent enzyme exhibited a greater affinity for histones than did the cyclic AMP-dependent enzyme in the presence of Mg2+.
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PMID:Purification and general properties of guanosine 3':5'-monophosphate-dependent protein kinase from guinea pig fetal lung. 17 61

A nucleoside-dependent protein kinase (EC 2.7.1.37) was partially purified from Trypanosoma gambiense, the pathogenic agent of sleeping sickness. This enzyme catalyzes the phosphorylation of histone and protamine. Various nucleosides at the concentration of 10(-4) M stimulated the histone kinase activity about two-fold, whereas cyclic AMP and cyclic GMP were without effect. The pH-optimum for histone phosphorylation was at about pH 7.0. The enzyme activity absolutely depends on Mg2+, Mn2+ or Co2+. The apparent Km-value for histone was 0.3 mg/ml and those for ATP were 2 - 10(-4) M and 6 - 10(-5) M in the absence or presence of 10(-4) M adenosine respectively. IDP and ADP complete with ATP. The inhibition constants were calculated to be 2 - 10(-4) M and 2.5 - 10(-4) M, respectively. The molecular weight of the histone kinase was found to be 95 000 by gel filtration and 88 000 by sedimentation in a sucrose gradient.
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PMID:Nucleoside-dependent protein kinase from Trypanosoma gambiense. 17 63

The stimulatory and inhibitory activities in the crude preparation of protein kinase modulator from dog heart were separated by Sephadex G-100 gel filtration, and the stimulatory modulator was further purified by DEAE-cellulose chromatography. The isolated stimulatory modulator, as the crude modulator preparation, stimulated the activity of the purified guanosine 3':5'-monophosphate (cGMP)-dependent protein kinases of both mammalian and arthropod origins in the presence of cGMP. The cGMP-dependent protein kinases were not activated by cGMP in the absence of either the isolated stimulatory modulator or the crude modulator. The stimulatory modulator, unlike the crude modulator had no effect on the activity of adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase. The stimulatory modulator was a protein since its activity was destroyed by trypsin but was resistant to hydrolysis by DNase, RNase, phospholipase C, and lysozyme. The isolated inhibitory modulator, presumably the same as the protein inhibitor of cAMP-dependent protein kinase reported by Walsh et al. (Wash. D.A., Ashby, C.D., Gonzalez, C., Calkins, D., Fischer. E.H., and Krebs, E.G. (1971) J. Biol. Chem. 246, 1977-1985), depressed the cAMP-stimulated activity of cAMP-dependent protein kinase as did the crude preparation of protein kinase modulator. The isolated inhibitory modulator, unlike the crude preparation, was without effect on cGMP-dependent protein kinase. The present findings provide evidence to support that in mammals there are separate proteins for the stimulatory and the inhibitory activities of protein kinase modulator, in contrast to the modulator from an arthropod tissue (lobster tail muscle, Donnelly et al. (Donnelly, T.E., Jr., Kuo, J.F., Reyes, P.L., Liu, Y.P., and Greengard, P. (1973) J. Biol. Chem. 248, 190-198) which has been shown to possess both activities.
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PMID:Isolation of stimulatory modulator of guanosine 3':5'-monophosphate-dependent protein kinase from mammalian heart devoid of inhibitory modulator of adenosine 3':5'-monophosphate-dependent protein kinase. 18 22

Although guanosine 3':5'-monophosphate (cyclic GMP)-dependent protein kinase (protein kinase G) which was partially purified from silkworm pupae was not dissociated by cyclic GMP into catalytic and regulatory subunits as described for adenosine 3':5'-monophosphate-dependent protein kinase (protein kinase A) (Takai, Y., Nakaya, S., Inoue, M., Kishimoto, A., Nishiyama, K., Yamamura, H., and Nishizuka, Y. (1976) J. Biol. Chem. 251, 1481-1487), limited proteolysis with trypsin resulted in the formation of catalytic and cyclic GMP-binding fragments which showed molecular weights of approximately 3.4 X 10(4) and 3.6 X 10(4), respectively (the molecular weight of native protein kinase G was 1.4 X 10(5)). The catalytic fragment did not bind cyclic GMP and was fully active in the absence of the cyclic nucleotide. The fragment did not show an absolute requirement for a sulfhydryl compound and high concentrations of Mg2+ (50 to 100 mM), both of which were necessary for the maximal activation of native protein kinase G. The catalytic fragment was not inhibited by the cyclic GMP-binding fragment nor by the regulatory subunit of protein kinase A. Inversely, the cyclic GMP-binding fragment was unable to inhibit the catalytic subunit of protein kinase A. Protein inhibitor, which was described for protein kinase A, was inert for the catalytic fragment.
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PMID:Guanosine 3':5'-monophosphate-dependent protein kinase from silkworm, properties of a catalytic fragment obtained by limited proteolysis. 18 28

The non-histone chromosomal protein fraction isolated from purified brain nuclei possesses protein kinase activity. 93% of this activity is lost by heating at 80 degrees C for 5 min. cAMP does not affect the reaction, but cGMP is inhibitory. In the presence of S-100, an acidic brain-specific protein, phosphate incorporation is enhanced 3 to 4 fold. Bovine serum albumin has no effect whereas histone inhibits activity.
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PMID:Nuclear protein kinase of brain: effect of S-100 protein. 18 May 74

The crude protein kinase modulator preparations obtained from several rat tissues (aorta, brain heart, liver, lung, skeletal muscle, small intestine and testis) were separated into their stimulatory and inhibitory modulator components by Sephadex G-100 gel filtration. The isolated stimulatory modulator augmented the activity of guanosine 3':5'-monophosphate-dependent protein kinase. The isolated inhibitory modulator, on the other hand, depressed the activity of cyclic AMP-dependent protein kinase; it was without effect on the activity of cyclic GMP-dependent protein kinease. The present findings indicate that in the mammal, apparently in contrast to the arthropoda, separate proteins are responsibile for the stimulatory and the inhibitory activities of protein kinase modulator and that the two classes of cyclic nucleotide-dependent protein kinase are regulated in an opposing manner by these two types of modulators.
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PMID:Stimulatory modulator of guanosine 3':5'-monophosphate-dependent protein kinase from mammalian tissues. 18 Oct 72

Several cyclic nucleotide derivatives with aminoalkyl side chains attached to the purine ring were synthesized and their interactions with adenosine 3',5'-monophosphate (cAMP) dependent protein kinase were studied before and after immobilization to CNBr-activated Sepharose 4B. The soluble N6-substituted derivatives were as effective as cAMP itself in activating protein kinase and were more effective than 8-substituted cAMP derivatives, whereas the 2-substituted cAMP derivatives and the cGMP derivatives were the least effective. All of the synthetic derivatives tested were poor substrates for beef heart phosphodiesterase being hydrolyzed at rates less than 2% for that of cAMP itself. Utilizing methodology developed to evaluate the affinity of protein kinase for immogilized cyclic nucleotides it was found that all of the immobilized cyclic nucleotides interacted with protein kinase in a biospecific manner as judged by the following criteria: (1) the immobilized cyclic nucleotides competed with cAMP for the binding sites on protein kinase; (2) the analogous spacer-arm did not compete; and (3) the effects of enzyme concentration, MgATP, and cleavage of the cyclic phosphate ring on the interactions of protein kinase with the immobilized cyclic nucleotides were the same as previously shown for free cAMP. In addition, the immobilized ligands were bound with the same order of effectiveness as the analogous soluble ligand. The observed Ka for the activation of 0.005 muM protein kinase by N6-H2N(CH2)2-cAMP was increased from 0.23 to 3 muM by the process of immobilization. This increase was unaffected by the coupling density and spacer-arm length. The observed Kb for 0.10 muM protein kinase binding to immobilized N6-H2N(CH2)2-cAMP was increased as the molecular sieving exclusion limit of the matrix used was decreased indicating that at least part of this decrease in apparent affinity upon immobilization is due to exclusion of the enzyme from a portion of the matrix and therefore of the immobilized ligand molecules.
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PMID:Binding of adenosine 3',5'-monophosphate dependent protein kinase regulatory subunit to immobilized cyclic nucleotide derivatives. 18 16

In this work the kinetics of activation of the cyclic AMP-dependent protein kinase by several catecholamines and ACTH, have been studied in rat epididymal fat pads and isolated fat cells. The method of Soderling and co-workers which permits the measurement of the state of activation of the protein kinase after hormonal stimulation in adipose tissue, has been used. Kinetics experiments where norepinephrine was used showed that the results obtained with isolated cells conform to the models of Sutherland and Brostrom and co-workers. Wtih intact tissue, norepinephrine not only stimulates the protein kinase activity measured without exogenous cyclic AMP but also the total activity measured in the presence of cyclic AMP (5 X 10(-6) M); thus the effect of norepinephrine, obtained during incubation of the tissue, and that of cyclic AMP, added to the soluble fraction after incubation, were additive. This effect seems to be of the beta type because it is blocked completely by propranolol. A weak, additive but significant effect was also obtained with epinephrine and isoproterenol but not with ACTH. Neither cyclic GMP nor cyclic IMP seems implicated in this effect. It was shown that stroma vascular cells which are present in the fat pads are not involved. These results suggest that the effects of norepinephrine on the protein kinase of the fat pads cannot be completely explained by the model of Brostrom and colleagues.
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PMID:Additive effects of norepinephrine and cyclic AMP on the activation of the protein kinase from adipose tissue. 18 9


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