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)

cAMP-dependent protein kinase activity was present in a soluble TSH receptor fraction. The Km of this enzyme was 2.2 X 10(-6) M for casein substrate in the absence or presence of 10(-5) M cAMP. A [3H]cAMP-binding protein was also found in this fraction. The Ka for [3H]cAMP-binding was 0.11 X 10(6) M-1, with a total binding capacity of 3 nmol/mg protein. After fractionation using a continuous sucrose density gradient, one of the several [125I]iodobovine TSH-binding peaks corresponded to a [3H]cAMP-binding peak. After fractionation on a sucrose density gradient containing 0.4 M NaCl at pH 6.5, a major peak of protein kinase activity was shown. This protein kinase activity was stimulated by adding 10(-5) M cAMP. A peak of [3H]cAMP-binding activity corresponded to the same peak. Protein kinase activity in the receptor fraction was stimulated by adding 6 mg/ml bovine TSH. The soluble TSH receptor fraction also has an adenylate cyclase activity stimulated by TSH. These results suggest that some TSH receptors released from thyroid plasma membranes have associated adenylate cyclase activity and cAMP-dependent protein kinase activity. The receptor, cyclase, and kinase activities may exist in a functional primary receptor unit which is spontaneously released from plasma membranes.
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PMID:Adenosine 3',5'-monophosphate-dependent protein kinase activity in soluble thyrotropin receptor complex. 22 Nov 90

The effect of catecholamines on membrane-associated protein kinase in the mature human erythrocyte was investigated. Protein kinase activity was assayed after isolation of membranes from intact erythrocytes incubated with and without catecholamines. Activation of the enzyme is expressed as the ratio of the extent of phosphorylation of exogenous protein substrate in the absence to that in the presence of 2.5 microM cyclic AMP (cAMP). The potent beta-adrenergic agonist, (-)isoproterenol (2 microM), (-)epinephrine (10 microM) and (-)norepinephrine (10 microM) stimulated the cAMP-dependent protein kinase in membranes, 38 +/- 7%, 31 +/- 6%, and 30 +/- 6%, respectively. Maximal stimulation of membrane protein kinase by 10 microM (-)epinephrine was obtained approximately equal to 30 min after initiation of the incubation of erythrocytes with the hormone. The concentrations of (-)catecholamines that gave half-maximal stimulation of the membrane protein kinase were 0.17 microM for isoproterenol, 0.35 microM for epinephrine, and 0.63 microM for norepinephrine. The membrane protein kinase response to beta-adrenergic agonists was found to be stereospecific. The stimulation of membrane protein kinase by 10 microM (-)epinephrine was inhibited by the beta-adrenergic antagonist, (-)propranolol with EC50 = 0.60 microM, and the inhibition of agonist stimulation of the cAMP-dependent protein kinase by propranolol was stereospecific. These studies suggest that a functional beta-adrenergic receptor exists in the mature human erythrocyte.
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PMID:Catecholamine regulation of human erythrocyte membrane protein kinase. 22 12

Protein kinase activity (ATP:protein phosphotransferase, EC 2.7.1.37) has been found associated with the D2 hybrid protein, a highly purified protein of 107,000 daltons specified by the adenovirus-simian virus 40 (SV40) hybrid Ad2(+)D2, which has many properties associated with authentic SV40 T antigen [Tjian, R. & Robbins, A. (1979) Proc. Natl. Acad. Sci. USA 76, 610-614]. We have now examined some of the biochemical characteristics of the reaction products. Acceptors for the terminal phosphoryl group of [gamma-(32)P]ATP are the purified protein itself and at least four proteins extracted from nuclei of uninfected cells. Purified histones do not serve as substrate for the enzyme. Phosphorylation is markedly reduced by heating the D2 hybrid protein to 50 degrees C for 30 min. The products of phosphorylation are stable to treatment with ethanol/ether, DNase, and RNase, but completely degraded by digestion with Pronase, demonstrating their protein nature. The phosphate bonds are liable to hot alkali and sensitive to digestion with alkaline phosphatase but stable to treatment with hot acid or hydroxylamine. These results provide evidence that (32)P is incorporated into O-phosphoserine or O-phosphothreonine residues of acceptor proteins, indicating that the enzymatic activity is characteristic for protein kinase, and that cell-specified nuclear proteins other than histones may serve as substrates for the enzyme.
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PMID:Protein kinase activity associated with the D2 hybrid protein related to simian virus 40 T antigen: some characteristics of the reaction products. 22 74

Two cyclic nucleotide-independent protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) have been purified to homogeneity from rat liver nuclei. While these enzymes have many similar catalytic properties (preference for acid rather than basic proteins), they differ in molecular weight and subunit composition. Protein kinase NII will utilize ATP and GTP as phosphate donors while protein kinase NI will only effectively use ATP. Both enzymes reveal an unusual activation by Fe2+.
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PMID:Properties of rat liver nuclear protein kinases. 22 67

DEAE-cellulose chromatography of the 105,000 X g supernatant fraction (cytosol) obtained from popped estrous rabbit follicles revealed the presence of a single form of cAMP-dependent protein kinase, designated protein kinase 3. The iv injection of an ovulatory dose of hCG to estrous rabbits promoted the appearance of a second, transient peak of cytosol cAMP-dependent protein kinase, protein kinase 1. Protein kinase 1 was detected within 10 min of hCG administration but had regressed to undetectable levels by 24 h in corpora lutea (CL) of pseudopregnancy and by 72 h in CL of pregnancy. Ovulation and subsequent CL formation were accompanied by the appearance of a third form of cAMP-dependent protein kinase, designated protein kinase 2. Protein kinase 2 was present within 2 h after hCG administration and persisted as a major form of cytosol cAMP-dependent protein kinase throughout the life span of CL. All three forms of protein kinase were inhibited by the heat-stable protein kinase inhibitor from rabbit skeletal muscle, possessed cAMP-binding activity, and were markedly stimulated by 10(-7) M cAMP. The activity of protein kinase 3 in CL of pregnancy, in corpora albicantia, and in interstitial tissue was markedly greater than that in follicles or in CL of pseudopregnancy, while the activity of protein kinase 2 remained relatively constant throughout the luteal life span. The iv injection of a luteolytic dose of hCG to 4-day pseudopregnant rabbits promoted no alterations of the protein kinase elution profile upon DEAE-cellulose chromatography of the luteal cytosol obtained 10 min to 3 days post-hCG injection. However, with dedifferentiation of corpora albicantia into interstitial tissue, the cAMP dependency of protein kinase 2 was reduced. The results indicate that the enzymatic activity and multiplicity of cAMP-dependent protein kinases in the cytosol of ovarian structures are subject to regulation by LH (hCG) and depend upon the various reproductive stages of the rabbit.
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PMID:Rabbit ovarian protein kinases. II. Effect of an ovulatory dose of human chorionic gonadotropin or luteinizing hormone on the multiplicity of follicular and luteal protein kinases. 57 Apr 95

The Y1 adrenocortical tumor cell mutants, Kin-7 and Kin-8, harbor point mutations in the regulatory subunit (RI) of the type 1 cAMP-dependent protein kinase (cAMPdPK) that render the enzyme resistant to activation by cAMP. These mutants also are resistant to many of the regulatory effects of ACTH and cAMP. In order to examine the causal relationships between the mutations in cAMPdPK and the resistance to ACTH and cAMP, the Kin mutants were transfected with expression vectors encoding wild type subunits of cAMPdPK in order to restore cAMP-responsive protein kinase activity. The transformants then were screened for the concomitant recovery of cellular responsiveness to ACTH and cAMP. In the mutant Kin-7, cAMP-responsive protein kinase activity was recovered after transfection with an expression vector encoding wild type mouse RI. Protein kinase activity in the mutant Kin-8 remained largely cAMP-resistant after transfection with the RI expression vector but could be rendered cAMP-responsive by transfection with an expression vector encoding the wild type catalytic subunit. The recovery of cAMP-responsive protein kinase activity was accompanied by the recovery of steroidogenic and morphological responses to ACTH and cAMP, suggesting that the cAMP-dependent signaling cascade plays an obligatory role in these actions of ACTH. The growth-regulatory effects of cAMP were not reversed with the recovery of cAMP-responsive protein kinase activity, suggesting that cAMP-resistant growth regulation results from second-site, adaptive mutations either in the original Kin mutant population or in the transformants. Studies on the conversion of 22(R)-hydroxycholesterol into steroid products in parent and mutant cells indicate that the Kin mutations reduce the steroidogenic capacity of the cell as well as inhibit the hormone- and cyclic nucleotide-dependent mobilization of substrate cholesterol.
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PMID:The causal relationship between mutations in cAMP-dependent protein kinase and the loss of adrenocorticotropin-regulated adrenocortical functions. 133 50

5,6-Dichloro-1-(beta-D-ribofuranosyl)benzimidazole (DiCl-RB) is a powerful inhibitor of casein kinase-2 (CK-2) [Zandomeni, R. et al. (1986) J. Biol. Chem. 261, 3414-3420]. Here a series of 17 analogues of DiCl-RB has been employed for studying the specificity and the mode of action of this family of CK-2 inhibitors. The two halogen substituents on the benzene ring are shown to play a prominent role in inhibition, the 5,6-dibromo derivative (DiBr-RB) being fivefold more effective than DiCl-RB (Ki = 2 microM, with GTP as substrate), whereas the difluoro derivative (DiF-RB) is nearly as ineffective as unsubstituted 1-(beta-D-ribofuranosyl)benzimidazole. On the other hand, although some modifications of the ribose group significantly decrease the inhibitory efficiency, the sugar moiety is not strictly required, since dichlorobenzimidazole itself (DiCl-Bz) is an inhibitor almost as good as DiCl-RB. Inhibition of CK-2 by DiCl-RB and by its analogues, DiCl-Bz included, is of the competitive type with respect to the nucleotide substrate, the Ki values being lower with GTP than with ATP. The Ki values of the most potent inhibitor, DiBr-RB, with ATP and GTP, are 6 microM and 2 microM, respectively, denoting an affinity for the enzyme higher than that of the physiological substrates, ATP and GTP. DiBr-RB has been assayed for its inhibitory capacity toward several protein kinase other than CK-2. Protein kinase-C, cAMP-dependent protein kinase, the Ser/Thr protein kinase expressed by Pseudorabies virus, and four different tyrosine protein kinases from spleen, proved insensitive to DiBr-RB concentrations capable of almost entirely suppressing the activity of rat liver and maize seedling CK-2. Casein kinase-1 however is nearly as sensitive as CK-2 to DiBr-RB. Inhibition of CK-1 is also of the competitive type with respect to ATP (Ki = 14 microM). Although the inhibitory spectrum of CK-1 by the various analogues is reminiscent of that observed with CK-2, a remarkable difference is revealed by 5'-phosphorylation of ribose which increases the Ki with CK-2 while decreasing that with CK-1.
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PMID:Ribofuranosyl-benzimidazole derivatives as inhibitors of casein kinase-2 and casein kinase-1. 210 15

The cause and effect relationship between mutations in cAMP-dependent protein kinase activity and resistance of adrenocortical tumor cells to ACTH and cAMP was evaluated by transfection with cloned cDNAs encoding subunits of the mouse cAMP-dependent protein kinase. Protein kinase defective, Kin 8 adrenocortical tumor cells were transfected with pRev [an expression vector encoding the regulatory subunit of the type 1 cAMP-dependent protein kinase (RI)] or with pC alpha ev [an expression vector encoding the catalytic subunit of cAMP-dependent protein kinase (C)]. The pC alpha ev transformant recovered cAMP responsive protein kinase activity, whereas the pRev transformant recovered cAMP-binding activity, but did not recover cAMP responsive protein kinase activity. The pC alpha ev transformant concomitantly recovered steroidogenic and morphologic responsiveness to ACTH- and 8-bromo-cAMP, whereas the pRev transformant remained resistant to these effects of the hormone and cyclic nucleotide. Since Kin 8 cells recovered their responsiveness to ACTH and 8-bromo-cAMP following transfection with pC alpha ev we suggest that the defect in cAMP-dependent protein kinase activity is directly responsible for the ACTH- and cAMP-resistant phenotype of the Kin 8 mutant.
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PMID:Recovery of responsiveness to ACTH and cAMP in a protein kinase-defective adrenal cell mutant following transfection with a protein kinase gene. 254 99

Adrenaline, cAMP and cAMP-dependent protein kinase modulate the slow inward Ca current by the same basic mechanism, presumably a phosphorylation of membrane proteins. Protein kinase also seems to play a role in the regulation of K outward currents, but not for the transient inward current.
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PMID:Cardiac membrane currents and energetic state. 258 42

Differentiation of human peripheral blood monocytes into macrophages was accompanied by induction of the regulatory subunit of cAMP-dependent protein kinase I as determined by photoaffinity labeling of cytosol proteins with 8-N3-[32P]cAMP and DEAE-Sephacel chromatography. The appearance of cAMP-dependent protein kinase I in macrophages was not due to translocation from the particulate fraction of monocytes. The regulatory subunit of cAMP-dependent protein kinase II was present in both monocytes and in vitro-differentiated macrophages. Protein kinase I in macrophages demonstrated higher affinity for 8-N3-cAMP (KD = 0.7 nM) than did protein kinase II from either monocytes (KD = 14.5 nM) or macrophages (KD = 4.9 nM). These studies demonstrate induction of the regulatory subunit of cAMP-dependent protein kinase I during the differentiation of a normal human cell and support the hypothesis that cAMP may regulate some stages of differentiation.
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PMID:Induction of cAMP-dependent protein kinase I during human monocyte differentiation. 298 23


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