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)

Incubation of rat adipocytes with the same range of noradrenaline concentrations that stimulate lipolysis caused a rapid and stable decrease in the activity of fatty acyl-CoA synthetase. Corticotropin, glucagon and dibutyryl cyclic AMP also decreased the activity of the enzyme. The effect of noradrenaline was apparent over a wide range of concentrations for the three substrates of the enzyme. A novel fluorescence assay of fatty acyl-CoA synthetase using (1,N6-etheno)-CoA is described. The effect of noradrenaline was not abolished by inclusion of albumin in homogenization buffers, persisted through subcellular fractionation and isolation of microsomes (microsomal fractions) and even survived treatment of microsomes with Triton X-100. The effect of noradrenaline was rapidly reversed within cells by the subsequent addition of insulin or propranolol. The inclusion of fluoride in homogenization buffers did not alter the observed effect of noradrenaline. Additions of cyclic AMP-dependent protein kinase to adipocyte microsomes caused considerable phosphorylation of microsomal protein by [gamma-32P]ATP, but did not affect the activity of fatty acyl-CoA synthetase.
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PMID:Reversible inactivation by noradrenaline of long-chain fatty acyl-CoA synthetase in rat adipocytes. 388 97

Preparations of cytoskeleton from Y-1 cells were found to phosphorylate various cytoskeletal proteins when incubated with [gamma-32P]ATP. When cAMP was added to the cytoskeleton, a rapid increase in phosphorylation of cytoskeletal protein was observed, and changes were seen in the phosphorylation of individual proteins; four additional proteins were phosphorylated (mol wt, 165,000, 92,000, 45,000, and 24,000) and three proteins were more intensely phosphorylated than without cAMP (mol wt, 125,000, 51,000, and 38,000). In addition, one protein (mol wt, 96,000) that was intensely phosphorylated without cAMP was not phosphorylated with the cyclic nucleotide, and a second (mol wt, 48,000) was less phosphorylated. The increased level of total phosphorylation returned to the unstimulated level within 10 min. The increased phosphorylation of proteins produced by cAMP was inhibited by protein kinase inhibitor. cAMP-dependent protein kinase activity was closely associated with the cytoskeleton, since it was not removed by Triton X-100 (1%, wt/vol), although some activity could be extracted with buffer containing high concentrations of salt. When the cytoskeleton of Y-1 cells was subjected to treatments that disrupt the cytoskeleton before the cells were extracted (cytochalasin B, colchicine, and sonication), no change was seen in cAMP-dependent protein kinase activity. However, cytochalasin B increased phosphorylation of two proteins that were not phosphorylated by cAMP-dependent kinase (mol wt, 63,000 and 43,000). Sonication of the cytoskeleton before addition of [gamma-32P]ATP caused a number of changes in cAMP-independent phosphorylation, but did not affect cAMP-dependent phosphorylation. cAMP-dependent phosphorylation required Mg2+ and was inhibited by Ca2+. It is concluded that the cytoskeleton of Y-1 cells contains bound cAMP-dependent protein kinase that phosphorylates certain cytoskeleton proteins. The cytoskeleton also contains one or more cAMP-independent kinase systems. It is suggested that the cAMP-dependent protein kinase described here may be important in the cytoskeletal responses to ACTH.
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PMID:Adenosine 3',5'-monophosphate-dependent protein kinase associated with the cytoskeleton of adrenal tumor cells. 406 35

The hormonal regulation of adenylate cyclase, cAMP-dependent protein kinase activation, and adrenocorticotropic hormone (ACTH) secretion was studied in AtT20 mouse pituitary tumor cells. Corticotropin releasing factor (CRF) stimulated cAMP accumulation and ACTH release in these cells. Maximal ACTH release was seen with 30 nM CRF and was accompanied by a 2-fold rise in intracellular cAMP. When cells were incubated with both 30 nM CRF and 0.5 mM 3-methylisobutylxanthine (MIX) cAMP levels were increased 20-fold, however, ACTH release was not substantially increased beyond release seen with CRF alone. The activation profiles of cAMP-dependent protein kinases I and II were studied by measuring residual cAMP-dependent phosphotransferase activity associated with immunoprecipitated regulatory subunits of the kinases. Cells incubated with CRF in the absence of MIX showed concentration-dependent activation of protein kinase I which paralleled stimulation of ACTH release. Protein kinase II was minimally activated. When cells were exposed to CRF in the presence of 0.5 mM MIX there was still a preferential activation of protein kinase I, although 50% of the cytosolic protein kinase II was activated. Complete activation of both protein kinases I and II was seen when cells were incubated with 0.5 mM MIX and 10 microM forskolin. Under these conditions cAMP levels were elevated 80-fold. CRF, isoproterenol, and forskolin stimulated adenylate cyclase activity in isolated membranes prepared from AtT20 cells. CRF and isoproterenol stimulated cyclase activity up to 5-fold while forskolin stimulated cyclase activity up to 15-fold. Our data demonstrate that ACTH secretion from AtT20 cells is mediated by small changes in intracellular levels of cAMP and activation of only a small fraction of the total cytosolic cAMP-dependent protein kinase in these cells is required for maximal ACTH secretion.
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PMID:Hormonal activation of the cAMP-dependent protein kinases in AtT20 cells. Preferential activation of protein kinase I by corticotropin releasing factor, isoproterenol, and forskolin. 608 93

A cAMP-dependent protein kinase occurs in the intermediate lobe of the rat pituitary gland and the ACTH-secreting tumor AtT-20/D16-16 derived from the mouse pituitary gland. Exposure of either tissue to drugs increasing cAMP production and hormone release (forskolin, cholera toxin, or isoproterenol in the case of the intermediate lobe; forskolin or isoproterenol in the case of the AtT-20 cells) increases the cAMP-dependent protein kinase activity of a tissue homogenate in the absence, but not in the presence, of added cAMP. The potencies of these drugs to induce changes in the protein kinase activity ratio (i.e. enzyme activity in the absence of cAMP to enzyme activity in the presence of 3 microM cAMP) are comparable with their potencies as stimulants of hormone secretion. In either tissue, A23187, a calcium ionophore that stimulates hormone release but not cAMP production, does not change the protein kinase activity ratio. In the case of the AtT-20 cells, dexamethasone blocks the release of ACTH simulated by either isoproterenol or forskolin, but does not alter the enhancement of protein kinase activity induced by these drugs. Conversely, dexamethasone does not block the A23187-stimulated release of ACTH. The data suggest that cAMP modulates (but does not trigger) hormone secretion from the rodent pituitary gland by a mechanism involving activation of the cAMP-dependent protein kinase. Several possible sites for this modulatory effect of cAMP are discussed.
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PMID:Adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase activity in rodent pituitary tissue: possible role in cAMP-dependent hormone secretion. 609 42

The incorporation of [gamma-32P]ATP into proteins of rat brain polyribosomes was studied in vitro. The effects of cyclic nucleotides, calcium, hemin, ACTH, GTP, and spermine were examined. The incorporation of phosphate into proteins increased with time and phosphatase activity was very low; thus, the extent of phosphorylation was predominantly a reflection of protein kinase activity. Phosphorylation of proteins was not sensitive to Ca2+ in the presence or absence of either calmodulin or phosphatidylserine. Phosphorylation was also unaffected by cyclic nucleotides in the absence of exogenous enzymes. However, addition of a cAMP-dependent protein kinase together with cAMP resulted in a stimulation of the incorporation of phosphate into 4 phosphoproteins (pp70, pp58, pp43, and pp32); phosphorylation of pp32 was completely dependent on the addition of the kinase. ACTH (1-24), (11-24), and spermine inhibited the endogenous phosphorylation of one protein band (pp30). The phosphorylation of this 30 kD band was also selectively increased by hemin (5 microM). Higher concentrations of hemin exerted an inhibitory effect on the majority of the phosphoproteins. Protein phosphatase activity was not influenced by ACTH or spermine. The specific inhibition of pp30 phosphorylation by ACTH or spermine is most probably explained by an interaction with a cyclic nucleotide- and Ca2+ -independent protein kinase.
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PMID:Cyclic nucleotide- and calcium-independent phosphorylation of proteins in rat brain polyribosome: effects of ACTH, spermine, and hemin. 609 30

Y1 mouse adrenal tumor cells and mutants of Y1 cells (Kin 2 and Kin 8), with defects in regulatory subunit of type 1 protein kinase (R1), were assayed for steroid, growth, and plasminogen activator after application of the tumor promoter 12-O-Tetradecanoylphorbol-13-acetate (TPA). TPA, like ACTH, caused an increase in steroid production and a decrease in growth in Y1 cells. The effects on steroidogenesis were diminished in Kin 2 and markedly diminished in Kin 8. TPA induced plasminogen activator in Y1 but not Kin 2 or Kin 8 while ACTH induced the enzyme in both Y1 and Kin 2 but not Kin 8. TPA did not produce a measurable increase in cyclic nucleotides in Y1 cells. Unlike Cytochalasin E, another agent that causes steroidogenesis without changes in cyclic AMP concentration, TPA and ACTH did not require serum for its effect on steroid production. Cytochalasin E also caused induction of plasminogen activation in Y1, but not in Kin 2 or Kin 8 cells. TPA however produced growth inhibition in both mutant cell types while ACTH produced a progressively diminishing growth inhibitory effect in Kin 2 and Kin 8. The results suggest that a portion of TPA action on Y1 cells requires R1.
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PMID:Action of 12-O-tetradecanoylphorbol-13-acetate on Y1 adrenal cells apparently requires the regulatory subunit of type 1 cyclic AMP dependent protein kinase. 610 Sep 78

The ability of hormones to activate responses in a variety of tissues decreases with age. The mechanism(s) responsible for these alterations are unclear. We have confirmed that the ability of a beta-adrenergic receptor agonist to activate lipolysis in isolated rat adipocytes decreases with age. Maximum response to isoproterenol was greater in 2-mo-old rats (600 +/- 30 nmol of glycerol released/10(5) cells per h) than 12-mo-old rats (250 +/- 25 nmol/10(5) cells per h), P less than 0.001. Similarly, ACTH is less effective in activating lipolysis in the adipocytes from the older rats. However, the cAMP analogue 8-(4-chlorophenothio)adenosine 3',5'-monophosphate cyclic activated lipolysis equally in the two groups, suggesting that the deficit in adipocytes from the older rats was proximal to cAMP-dependent protein kinase activation. Both isoproterenol and ACTH were significantly less effective in promoting cAMP accumulation in adipocytes isolated from 12-mo-old rats. There was no difference in phosphodiesterase activity of the adipocytes between the two groups. beta-Adrenergic receptors were measured using the antagonist radioligand [125I]cyanopindolol. The number of beta-adrenergic receptors was actually increased in the adipocytes from 12-mo-old rats (26,000 +/- 2,600 receptors/cell) compared with cells from 2-mo-old rats (7,200 +/- 1,300 receptors/cell). The results suggest that diminished cAMP production is responsible for the diminished lipolytic response in the adipocytes of older rats. The mechanism responsible for this change is uncertain but cannot be explained by a loss in beta-adrenergic receptors.
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PMID:Age-related decrement in hormone-stimulated lipolysis. 615 Jun 43

Antisera have been produced against purified soluble cyclic guanosine monophosphate (cGMP) dependent-protein kinase (ATP: protein phosphotransferase EC 2.7.1.37) isolated from bovine lung. No cross-reactivity was observed between the antisera and structurally related components of cAMP-dependent protein kinases (cAMP kinase), as judged by the immunodiffusion and immunoprecipitation techniques. Immunocytochemical specificity was determined by absorption of antisera with pure antigen. The distribution of cGMP kinase has been examined in several rat tissues, using an indirect immunofluorescence technique, and compared with the immunocytochemical distribution of cGMP. In skeletal muscle, cGMP kinase was localized primarily to A bands on the muscle fiber and along the Z line in I band regions. Densitometric determinations of immunoperoxidase staining indicated that absorbance over A band areas was greater than absorbance over the I band regions. In small intestine, cGMP kinase is distributed primarily along the villus brush border membrane. In testis, cGMP kinase is observed in several cell types adjacent to the seminiferous tubular wall, including Sertoli cells and spermatogonia, as well as in association with meiotic chromosomes of pachytene spermatocytes. In the cortex of the adrenal glands from dexamethasone-suppressed rats, chronic ACTH treatment induced an increase in cGMP kinase fluorescence in nuclei. In each of the tissues examined, a striking correlation was observed between the distribution of cGMP kinase and cGMP, supporting the hypothesis that cGMP-mediated actions occur via cGMP kinases.
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PMID:Immunocytochemical localization of cyclic guanosine monophosphate-dependent protein kinase in endocrine tissues. 617 21

NPS(o-nitrophenyl sulfenyl)-ACTH stimulated steroidogenesis in Y1 cells to the same maximum level as did ACTH, but with a 60-fold lower potency than the native hormone. NPS-ACTH also stimulated the extracellular accumulation of cAMP in Y1 cells with lower potency than the unmodified hormone. The amount of cAMP accumulated in the presence of NPS-ACTH approached 75% of the maximum with ACTH. In Y1 plasma membranes, NPS-ACTH was a partial agonist of adenylate cyclase activity, witn an efficacy dependent upon the type of guanyl nucleotide present. The steroidogenic responses of two Y1(Kin) mutants and two Y1(Cyc) mutants to NPS-ACTH paralleled their responses to ACTH and reflected closely their defects in cAMP-dependent protein kinase and ACTH-sensitive adenylate cyclase activity. These data imply an obligatory role for adenylate cyclase and cAMP-dependent protein kinase activities in stimulation of steroidogenesis in Y1 cells by NPA-ACTH.
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PMID:Responses of Y1 adrenocortical tumor cells to o-nitrophenyl sulfenyl ACTH. 624 80

In Y1 adrenocortical tumor cells, corticotropin (ACTH), cyclic AMP, and 8-bromoadenosine 3',5'-monophosphate (8BrcAMP) stimulated ornithine decarboxylase activity (L-ornithine carboxy-lyase, EC 4.1.1.17) and steroidogenesis. The concentrations required for half-maximal activation of ornithine decarboxylase were 60 pM for ACTH and 1 mM for 8BrcAMP; the concentrations required for half-maximal activation of steroidogenesis were 50 pM for ACTH and 0.2 mM for 8BrcAMP. Ornithine decarboxylase activity increased 1.5 hr after the addition of these agents, reached a maximum between 4 and 6 hr, and then declined. Mutant clones with impaired ACTH-responsive adenylate cyclase systems [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]did not respond to ACTH with increased ornithine decarboxylase activity, but they responded normally to added cyclic AMP. These results indicate that adenylate cyclase and cyclic AMP are necessary for the stimulation of ornithine decarboxylase activity by ACTH. In a series of Y1(Kin) mutants with altered cyclic AMP-dependent protein kinase activities (ATP:protein phosphotransferase, EC 2.7.1.37), the effects of ACTH on ornithine decarboxylase also were attenuated. These findings suggest that cyclic AMP-dependent protein kinase also plays a necessary role in the stimulation of ornithine decarboxylase activity by ACTH. The effects of ACTH on ornithine decarboxylase in the Kin mutants, however, were quantitatively different from the effects on steroidogenesis and did not closely reflect the degree of defect in cyclic AMP-dependent protein kinase activity. These differences suggest that the pathways of ACTH action leading to stimulation of steroidogenesis and ornithine decarboxylase activity diverge subsequent to activation of the protein kinase.
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PMID:Regulation of ornithine decarboxylase activity by corticotropin in adrenocortical tumor cell clones: roles of cyclic AMP and cyclic AMP-dependent protein kinase. 624 65


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