Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein kinase, phosphodiesterase and adenylate cyclase of plasma membrane of adipocytes and the effect of the feedback regulator (FR) on these three enzymes was measured and compared. The basal level ratio of adenylate cyclase to phosphodiesterase to protein kinase was 1:1.9:3.0. Epinephrine and/or FR alters this ratio. FR stimulated protein kinase activity up to 3 fold in the presence of a wide range of enzyme concentrations, 5-50 mug membrane protein/tube. The concentration of FR effective for stimulation of membrane protein kinase was much greater than that needed for inhibition of adenylate cyclase and phosphodiesterases. The inhibition by FR on adenylate cyclase was the most potent effect among the 3 enzymes. 1 U (or 2 U/ml) of FR inhibited 50% of the adenylate cyclase activity in a defined system. The maximum effective concentration of FR for stimulation of membrane protein kinase was greater than 10 U/ml. Histone type 11A was the best substrate for protein phosphorylation so far observed. The FR stimulatory effect was observed at all substrate concentrations used ranging from 1-5 mg/ml. A NaF concentration curve shows that 15 mM NaF gave maximum phosphorylation. The stimulatory effect of FR was observed both in the presence and absence of NaF. Protein kinase of adipocyte plasma membrane was mainly cAMP-independent. The effect of FR (20 U/ml) in stimulation of protein phosphorylation was much greater than that of cAMP (1 X 10(-6) M). The cAMP and FR effects seemed to be additive. Preincubation of plasma membrane with FR in the absence of ATP resulted in no decrease but slight increase in protein kinase activity. A shift in protein kinase, phosphodiesterase and adenylate cyclase ratios by FR suggests the regulatory role of FR in cAMP metabolism in adipocytes.
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PMID:Influence on adipocyte plasma membrane bound protein kinase by feedback regulator. 17 96

Plasma membranes prepared from rat renal cortex contain both a parathyroid hormone-sensitive adenylate cyclase and a potent proteolytic activity which degrades the hormone into peptide fragments. The degree and pattern of degradation was determined by subjecting incubation mixtures to gel filtration and ion exchange chromatography. Estimation of the degree of degradation by acid precipitation of the intact hormone was inadequate since metabolism of the hormone apparently generated acid-insoluble fragments. When parathyroid hormone was incubated with membrane fraction, the capacity of its stimulatory effect on adenylate cyclase decreased steadily. This decrease of PTH activitiy could be closely related to the degradation of intact hormone by the same membrane preparation. The adenylate cyclase and degradative activity appeared to exist in similar membrane structures since they could not be separated by centrifugation through sucrose density gradients. The degradation of the hormone could not be inhibited by Trasylol and pancreatic or soybean trypsin inhibitors and was only slightly inhibited by ribonuclease and benzamidine. Histone (1 mg per ml), on the other hand, was able to decrease the degradation of the hormone and prevent the loss of its activity. Radioimmunoassay of the incubation mixtures showed that the rapid degradation of both amino- and carboxy-terminal regions of the hormone was prevented by histone. The oxidized, inactive hormone was also degraded to the same extent by the renal cortical membrane. Furthermore, the degradative activity was also found in plasma membrane preparations of renal medulla and liver. This lack of hormone and tissue specificity suggests that similar degradative activity exists in all tissues and that caution should be exercised in estimating hormonal potency based on activation of adenylate cyclase.
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PMID:Interaction of parathyroid hormone with membranes of kidney cortex: degradation of the hormone and activation of adenylate cyclase. 119 1

Fertilized sea urchin eggs undergo a series of rapid and synchronized mitotic divisions. Extracts were made at various times throughout the first three mitotic divisions and assayed for phosphorylating activity toward histone H1. Histone H1 kinase (HH1K) undergoes a transient activation (8- to 10-fold increase) 20 min before each cleavage. The amplitude of the HH1K peak strongly depends on the synchrony of the egg population. Concomitant cytological observations show that the time-course of HH1K correlates with the time-course of nuclear envelope breakdown and of metaphase. This correlation is observed at each cell division cycle. HH1K from each of the three first mitoses show identical time- and concentration-dependence curves as well as identical dose-inhibition curves with 6-dimethylaminopurine and quercetin, suggesting that the same (group of) kinase(s) is (are) activated before each cleavage. Ionophore A23187 does not trigger, but inhibits, HH1K activation; however, partial activation of the eggs with ammonia at pH 9.0 (but not at pH 8.0) triggers the transient HH1K activation. Appearance of the HH1K cycle requires protein synthesis since it is completely abolished in emetine-treated eggs. Although cytochalasin B blocks egg cleavage, it does not inhibit HH1K activation nor nuclear divisions. A prolonged HH1K activation cycle is observed in eggs arrested in metaphase with colchicine or nocodazole. Despite the existence of a cycle in cAMP concentration during mitosis, forskolin, an activator of adenylate cyclase, does not modify the time-course of HH1K activation and of cell division. The cycling HH1K is independent of calcium-calmodulin, calcium-phospholipids, or cyclic AMP. It clearly resembles the mammalian "growth-associated histone kinase." The relationship between the transient activation of HH1K and the intracellular mitotic factors driving the cell cycle is discussed.
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PMID:Cyclic activation of histone H1 kinase during sea urchin egg mitotic divisions. 282 94

Protein kinase activity of lymphocytes isolated from human subjects was assayed using histone as substrate. The activity was stimulated about twofold by cyclic AMP and total enzyme activity, determined in the presence of cyclic AMP, was inhibited by 65% by the specific heat-stable inhibitor of cyclic AMP-dependent protein kinase. Histone phosphorylation was not stimulated by cyclic GMP in the presence of the inhibitor. Cyclic AMP-dependent protein kinase could be activated in vitro by incubating intact cells with isoproterenol or with forskolin and was reflected by a significant (P less than 0.05) increase in the protein kinase activity ratio. In contrast to these well-characterized adenylate cyclase activators, incubating cells for up to 2 hr in vitro in the presence of the specific beta-blocker propranolol had no significant effect on the amount of cyclic AMP-dependent protein kinase that was in the activated state. When compared in subjects between the ages of 21 and 74 years, lymphocyte protein kinase activity was unaltered by age or gender. These results indicate that cyclic nucleotide-dependent protein kinase is of the cyclic AMP-dependent variety in the human lymphocyte. A low amount of the cyclic AMP-dependent activity (about 15%) is in the already activated state in freshly isolated cells, and this is not further reduced by incubation in vitro or by beta-blockade. In contrast to previously reported changes in the capacity to synthesize cyclic AMP, lymphocyte protein kinase is unaltered by gender or age in human subjects.
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PMID:Lymphocyte protein kinase activity in cells from young and elderly men and women. 300 43

Two protein kinases (ATP: protein phosphotransferase, EC 2.7.1.37) were detected in disrupted cilia of Paramecium tetraurelia. One of the enzymes exhibited maximum activity at pH 6.0, required 4 mM Mg2+ for its maximum activity and was stimulated by cyclic AMP and cyclic GMP. Histone was a good exogenous protein substrate for this enzyme, but protamine sulfate was not. The other protein kinase showed a peak of activity at pH 8.0, required 10 mM Mg2+ for its maximum activity and was slightly inhibited by cyclic AMP and cyclic GMP. Protamine sulfate was a good exogenous substrate for this enzyme. The pH 8.0 activity partitioned preferentially with the axonemes, but the pH 6.0 activity was divided almost equally between the axonemes and the membranes. We also found indirect evidence for the presence in cilia of phosphoprotein phosphatase (phosphoprotein phosphohydrolase, EC 3.1.3.16) and adenyl cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) activity.
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PMID:Biochemical studies of the excitable membrane of Paramecium. IV. Protein kinase activities of cilia and ciliary membrane. 625 91

Histone deacetylases (HDACs) are enzymes that catalyze the removal of acetyl groups from lysine residues of histone and nonhistone proteins. Recent studies suggest that they are key regulators of many cellular events, including cell proliferation and cancer development. Human class I HDACs possess homology to the yeast RPD3 protein and include HDAC1, HDAC2, HDAC3, and HDAC8. While HDAC1, HDAC2, and HDAC3 have been characterized extensively, almost nothing is known about HDAC8. Here we report that HDAC8 is phosphorylated by cyclic AMP-dependent protein kinase A (PKA) in vitro and in vivo. The PKA phosphoacceptor site of HDAC8 is Ser(39), a nonconserved residue among class I HDACs. Mutation of Ser(39) to Ala enhances the deacetylase activity of HDAC8. In contrast, mutation of Ser(39) to Glu or induction of HDAC8 phosphorylation by forskolin, a potent activator of adenyl cyclase, decreases HDAC8's enzymatic activity. Remarkably, inhibition of HDAC8 activity by hyperphosphorylation leads to hyperacetylation of histones H3 and H4, suggesting that PKA-mediated phosphorylation of HDAC8 plays a central role in the overall acetylation status of histones.
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PMID:Negative regulation of histone deacetylase 8 activity by cyclic AMP-dependent protein kinase A. 1470 48