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)

cAMP-dependent protein kinase, Ca+2- and phospholipid-dependent protein kinase, and protein kinase inhibitor activity were examined in renal homogenates and 20,000 X g supernatant fractions of normal and Hyp mice. In both genotypes, 70% of total renal cAMP-dependent protein kinase activity was recovered in the soluble fraction in which the activity ratio (without cAMP to with cAMP) of the enzyme was 0.35. The requirement for cAMP was not different for protein kinase of normal and mutant littermates, with an apparent Km for cAMP of 0.05 microM in both genotypes. Furthermore, vitamin D and calcium deficiencies did not significantly affect cAMP-dependent protein kinase activity in normal and Hyp mouse kidney. The concentration of the heat-stable protein kinase inhibitor protein in the 20,000 X g supernatant fraction was identical in normal and Hyp kidney. Whereas protein kinase inhibitor levels were increased 1.8-fold by vitamin D and calcium deficiencies in normal mice (P less than 0.001), no such increase was detectable in Hyp mice. Ca+2- and phospholipid-dependent-protein kinase (protein kinase C) activity in the 20,000 X g supernatant fraction comprised 50% of the total activity of kidney homogenates of both normal and mutant mice. The initial rate of protein kinase C was increased 1.5-fold in kidney supernatants of Hyp mice (P less than 0.001). In contrast, protein kinase C was not significantly different from normal in supernatant fractions of heart, spleen, and liver prepared from Hyp mice. The present demonstration of abnormally high renal protein kinase C activity in Hyp mice may serve to explain the relationship between the previously reported renal defects in brush border membrane phosphate transport and vitamin D metabolism in the mutant strain and elucidate the nature of the primary defect in the Hyp mouse.
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PMID:Protein kinase activity and protein kinase inhibitor in mouse kidney: effect of the X-linked Hyp mutation and vitamin D status. 299 97

Chickens were raised for 6 weeks from the date of hatch under red light on a vitamin D-free diet; controls were given an oral vitamin D supplement. Vitamin D-deficient animals showed decreased total serum calcium concentration and decreased DNA content in epiphysis and kidney homogenates. In calcifying epiphysis, total carbonic anhydrase (CA) activity was decreased, but activity per microgram DNA was slightly increased and specific activity was double that of the controls. Polyacrylamide gel isoelectric focusing after preparation of the enzyme showed a picture similar to that seen after parathyroid hormone (PTH) administration in chicks; therefore, this could be considered a secondary hyperparathyroidism. The CA activation was not seen in the kidney which can be explained by induction of an endogenous inhibitor protein of the cyclic AMP-dependent protein kinase exclusively in the kidney in vitamin D deficiency. In an additional experiment, chickens were raised for 3 weeks from the date of hatch under red light on a vitamin D-free diet. Daily oral substitution by different vitamin D metabolites (1,25(OH)2D3, 25OHD3, 24,25(OH)2D3) over 7 days led to CA activation compared with controls probably by restoring protein kinase activity in the kidney. Our results show that CA activity is inversely correlated with serum calcium concentrations which is in agreement with a regulatory mechanism recently proposed by us.
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PMID:Effect of vitamin D status on the activity of carbonic anhydrase in chicken epiphysis and kidney. 314 17

Cyclic AMP-dependent protein kinase activity in supernatants of homogenates of kidneys from vitamin D-deficient chicks is decreased to 70% of the level measured in kidneys from normal chicks. Activity was restored to normal by oral administration of vitamin D or 1,25-dihydroxyvitamin D3 for 1 or 2 weeks. Both isozymes of cAMP-dependent protein kinase were reduced to the same extent by vitamin D deficiency. The decreased enzyme activity could not be accounted for by a shift to the particulate fraction nor by an increased requirement for cyclic AMP. A heat stable, trichloroacetic acid-precipitable, trypsin-labile inhibitor of protein kinase activity was identified and quantitated in kidneys from vitamin D-deficient chicks (16 to 26 units/mg of protein) and from those given vitamin D (2 to 6 units/mg of protein). The measured difference in inhibitor levels could not be attributed to differential stability in kidney homogenates from vitamin D-deficient or -repleted chicks. The observed increase in inhibitor level with vitamin D deficiency is not sufficient to account for the decrease in cyclic AMP-dependent protein kinase activity, suggesting that the total amount of this enzyme activity is reduced in vitamin D deficiency.
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PMID:Effect of vitamin D status on cyclic AMP-dependent protein kinase activity and its heat-stable inhibitor in chick kidney. 627 Jan 31

The purpose of these studies was to characterize the action of PTH and 1,25(OH)2D3 on the renal metabolism of 25(OH)D3 to 1,25(OH)2D3 and 24,25(OH)2D3. Renal metabolism of 25(OH)D3, adenylate cyclase, and protein kinase activity were measured using isolated renal slices from rats fed a vitamin D-deficient, low-calcium diet and thyroparathyroidectomized. PTH added to renal slices for 4 h in vitro maximally increased 1,25(OH)2D3 production by 67% and decreased 24,25(OH)2D3 production by 24% over the concentration range 0.05-5.0 U/ml. Parathyroid hormone (PTH) (0.05 U/ml) added to renal slices for 5 min produced a significant increase in tissue cAMP and a near-maximal increase in cAMP-dependent protein kinase activity. Preincubation of renal slices with 50 nM 1,25(OH)2D3 decreased renal 1,25(OH)2D3 production by 26% and increased 24,25(OH)2D3 production by 55%. 1,25(OH)2D3 also blocked the effect of PTH (5.0 U/ml) on renal 25(OH)D3 metabolism. However, PTH-stimulated adenylate cyclase and protein kinase activity was not blocked by preincubation with 1,25(OH)2D3. These studies demonstrate that PTH may act directly on the kidney to modulate renal 25(OH)D3 metabolism and that this action can be inhibited by 1,25(OH)2D3. This inhibition by 1,25(OH)2D3 occurs at a site distal to or separate from PTH-stimulated protein kinase activity.
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PMID:Effect of PTH and 1,25(OH)2D3 on renal 25(OH)D3 metabolism, adenylate cyclase, and protein kinase. 632 Jun 59

The in vitro incubation of chick renal cells with parathyroid hormone (PTH) resulted in the inhibition of Na+-dependent phosphate uptake when the cells were isolated from 1,25-dihydroxycholecalciferol 1,25-dihydroxycholecalciferol [1,25-(OH)2D3]-repleted chicks but not when the cells came from vitamin D-deficient animals. Na+-independent phosphate and Na+-dependent alpha-methylglucoside uptakes were not affected by PTH and the vitamin D status of the bird. The activation of chick renal cell adenylate cyclase by PTH was significantly blunted when the enzyme was from vitamin D-deficient animals relative to the activation of the enzyme from repleted cockerels. This alteration was due to a change in maximum velocity of the system rather than an effect on the affinity for hormone. The response of adenylate cyclase to other hormones, e.g., prostaglandin E2, and activators, e.g., 5' -guanylyl-imidodiphosphate and forskolin, was not affected by the vitamin D status of the animal. PTH had little effect in activating protein kinase in cells from vitamin D-deficient chicks. In cells from vitamin D-sufficient birds, PTH caused a fourfold increase in adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. Dibutyryl cAMP inhibited Na+-dependent phosphate uptake by cells from 1,25-(OH)2D3-repleted animals, but the cyclic nucleotide had no effect on phosphate uptake in cells from vitamin D-depleted chicks. This finding suggests that the loss of PTH receptor sites known to be concomitant with the secondary hyperparathyroidism associated with vitamin D deficiency is only a partial explanation for the failure of PTH to inhibit phosphate uptake in cells from vitamin D-deficient animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Responses of chick renal cell to parathyroid hormone: effect of vitamin D. 654 26

We have studied two proteins potentially involved in the regulation of the 25-OH-D-1-hydroxylase, which is located in the renal mitochondria and which is responsible for the production of the steroid hormone 1,25(OH)2D3. The endogenous inhibitor of cyclic AMP-dependent protein kinase, PKI, is down regulated by 1,25(OH)2D3. Having cloned and sequenced PKI cDNA, we studied its message levels and found them to be regulated by 1,25(OH)2D3 tissue specifically in the kidney and in kidney cell culture. In other experiments we over expressed the ferredoxin component of the 1-hydroxylase and found it to be physically and chemically indistinguishable from those of classic steroidogenic tissues. The mRNA encoding the ferredoxin component is up-regulated by chronic vitamin D deficiency, which at the same time leads to sustained elevation in 1-hydroxylase activity; no short term effect of 1,25(OH)2D3 on ferredoxin mRNA in kidney cell culture could be demonstrated. Finally, there was an association between decreased phosphorylation of ferredoxin and decreased 1-hydroxylase activity brought about by treatment of cultured kidney cells with TPA. Control of the renal signaling events involved in the production of 1,25(OH)2D3 remains a fruitful area of investigation in the field of the metabolism and actions of vitamin D and its metabolites.
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PMID:Regulation of the ferredoxin component of renal hydroxylases at transcriptional and postranslational levels and of the protein inhibitor of cyclic AMP-dependent kinase. 762 15

The vitamin D hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is generated by a series of hydroxylation steps in the liver and kidneys. We investigated whether naturally vitamin D-deficient subterranean mammals (naked mole rats, Heterocephalus glaber) employ the same enzymatic pathways, and whether these are regulated in a similar manner to that established for other mammals. Vitamin D3-25-hydroxylase in the liver and both 25-hydroxyvitamin D3-1-hydroxylase and 25-hydroxyvitamin D3-24 hydroxylase (1-OHase and 24-OHase) in the kidney were detectable in mole rats. As expected for vitamin D-deficient mammals, the 1-OHase activity predominated over the 24-OHase. After mole rats received a supraphysiological supplement of vitamin D3, 1-OHase activity was suppressed and 24-OHase activity was enhanced. Irrespective of vitamin D status, forskolin (a protein kinase A activator) and dibutyryl cyclic AMP did not alter the activity of either 1-OHase or 24-OHase. These findings suggest that the response of renal hydroxylases to parathyroid hormone was blunted. Phorbol esters, 12-O-tetradecanoylphorbol 13-acetate (TPA) and 1-oleoyl-2-acetylglycerol (OAG) (protein kinase C activators), suppressed 1-OHase activity. 24-OHase activity was induced by TPA but not by OAG. These effects were similar to those illicited by vitamin D3 supplementation but were additive in that they increased the responses shown in vitamin D-replete mole rats. These data confirm that naturally vitamin D-deficient mole rats can convert vitamin D3 to the hormone, 1,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vitamin D hydroxylases and their regulation in a naturally vitamin D-deficient subterranean mammal, the naked mole rat (Heterocephalus glaber). 785 93

The 1,25-dihydroxyvitamin D3 receptor becomes phosphorylated upon treatment with 1,25-dihydroxyvitamin D3. We have investigated the role of phosphorylation in the transcriptional activity induced by 1,25-dihydroxyvitamin D3 through its receptor. An active 1,25-dihydroxyvitamin D3-dependent transcription system was reconstituted in CV-1 cells by co-transfection of plasmids containing the rat 1,25-(OH)2D3 receptor DNA and a functional vitamin D response element (DRE) in a reporter gene construct. Treatment of these transiently transfected CV-1 cells with modulators of protein kinase A (8-Br-cAMP, PKIA and H-9) and phosphatases (Okadaic acid) resulted in mimicking or abolishing the transcriptional activity of 1,25-dihydroxyvitamin D3 in a receptor-dependent fashion. These modulators directly altered 1,25-dihydroxyvitamin D3 receptor phosphorylation. Therefore, the present results strongly suggest that phosphorylation plays a central role in the transcriptional activity of the 1,25-dihydroxyvitamin D3 receptor.
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PMID:Phosphorylation is involved in transcriptional activation by the 1,25-dihydroxyvitamin D3 receptor. 838 84

Hepatocyte growth factor (HGF) secreted from human promyelocytic leukemia cell line, HL-60, is indistinguishable from HGF in human plasma and its release is significantly stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), a differentiation-inducer of HL-60 cells into monocytes/macrophages (Nishino T et al: Biochem Biophys Res Commun 181:323, 1991). TPA stimulated HGF release from the cells through an activation of C-kinase, but not through a formation of reactive oxygen species. Furthermore, dibutyryl cAMP (dbcAMP), an activator of A-kinase and granulocyte-inducer, also stimulated HGF release. 1,25-Dihydroxyvitamin D3, another monocyte/macrophage-inducer, abated either TPA- or dbcAMP-stimulated synthesis and release of HGF in a dose-dependent manner probably via its nuclear receptor as reflected by vitamin D analog study. The effects of these three reagents on the steady-state levels of HGF mRNA of 6.0 kb corresponded with their effects on its protein levels. Furthermore, a close correlation between intracellular and extracellular HGF levels strongly suggested that these reagents affected HGF release mainly on its synthesis step. Recombinant human HGF significantly stimulated the proliferation and alkaline phosphatase activity of mouse osteoblastic cell line, MC3T3-E1. In summary, HL-60 cells secrete HGF, whose synthesis is specifically regulated by various reagents independent of their differentiation-inducing effects. Because HGF shows a direct effect on osteoblast-like cells, it might be involved in the interaction of bone marrow cells with bone cells.
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PMID:Regulation of release of hepatocyte growth factor from human promyelocytic leukemia cells, HL-60, by 1,25-dihydroxyvitamin D3, 12-O-tetradecanoylphorbol 13-acetate, and dibutyryl cyclic adenosine monophosphate. 839 78

We analyzed the endogenous nuclear 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) receptor (VDR) in rat osteosarcoma (ROS 17/2.8) cells and present biochemical evidence that it is a phosphoprotein. When ROS 17/2.8 cells are labeled metabolically with [35S]methionine, treatment with 10(-8) M 1,25(OH)2D3 elicits a decrease in the electrophoretic mobility of immunoprecipitated VDR in denaturing polyacrylamide gels, a property characteristic of phosphorylated proteins. Similar labeling of cells with [32P]orthophosphate results in a rapid (< or = 30 min), 1,25(OH)2D3-dependent incorporation of 32P into a 54-kDa VDR species that comigrates with the slower migrating receptor species extracted from [35S]methionine-labeled ROS 17/2.8 cells that have been exposed to 1,25(OH)2D3. Alkaline phosphatase treatment of immunoprecipitated VDR from 1,25(OH)2D3-treated cells converts the form of the VDR with reduced mobility to the faster migrating species present in 1,25(OH)2D3-deficient cells. Incubation of ROS 17/2.8 cells with the non-hypercalcemic 1,25(OH)2D3 analog, 22-oxacalcitriol (OCT), produces a level of VDR phosphorylation similar to that elicited by 1,25(OH)2D3 treatment. Transient transfection of osteosarcoma cells with a reporter vector containing a vitamin D responsive element derived from the rat osteocalcin gene yields equivalent transcriptional activation in the presence of either 1,25(OH)2D3 or OCT. Further experiments performed at various 1,25(OH)2D3 concentrations to assess the relationship between receptor phosphorylation and transcriptional activity in intact cells showed a positive correlation between these two parameters, indicating that the 1,25(OH)2D3 hormone stimulates VDR phosphorylation and transcriptional activation in parallel. Finally, highly purified casein kinase II (CK-II) phosphorylates the VDR in a 1,25(OH)2D3-independent, in vitro reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The 1,25-dihydroxy-vitamin D3 receptor is phosphorylated in response to 1,25-dihydroxy-vitamin D3 and 22-oxacalcitriol in rat osteoblasts, and by casein kinase II, in vitro. 839 28


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