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 actions of parathyroid hormone (PTH) on the renal cortex are thought to be mediated primarily by cAMP-dependent protein kinase (PKA) with some suggestion of a role for protein kinase C (PKC). However, present methods for assaying PKA and PKC in subcellular fractions are insensitive and require large amounts of protein. Recently, a sensitive method for measuring the activity of protein kinases has been reported. This method uses synthetic peptides as substrates and a tandem chromatographic procedure for isolating the phosphorylated peptides. We have adapted this method to study the effect of PTH on PKA and PKC activity using thin slices of rat renal cortex. PTH (250 nM) stimulated cytosolic PKA activity four- to fivefold within 30 s, and PKA activity was sustained for at least 5 min. PTH also rapidly stimulated PKC activity in the membrane fraction and decreased PKC activity in the cytosol. These changes were maximal at 30 s, but unlike changes in PKA, they declined rapidly thereafter. PTH significantly activated PKC only at concentrations of 10 nM or greater. This study demonstrates that PTH does activate PKC in renal tissue, although the duration of activation is much less than for PKA. It also demonstrates that a combination of synthetic peptides with tandem chromatography can be used as a sensitive assay procedure for protein kinase activity in biological samples.
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PMID:Effect of parathyroid hormone on rat renal cAMP-dependent protein kinase and protein kinase C activity measured using synthetic peptide substrates. 199 Sep 75

In previous work we have shown that parathyroid hormone (PTH) inhibits Na+/H+ exchange in cellular suspensions of OK (opossum kidney) cells (an established renal epithelial cell line) in a dose-dependent manner. PTH effects could be mimicked by pharmacological activation of both protein kinase A and protein kinase C (Helmle-Kolb et al. 1990). In the present paper we extend these observations and analyze the PTH-dependent control of Na+/H+ exchange in OK cells kept in epithelial configuration (monolayer). Na+/H+ exchange activity is examined by microfluorometry using the intracellularly trapped pH-sensitive dye 2'7'-bis-(2-carboxyethyl)-5,6-carboxyfluorescein. Cells recovered from an acid load (NH4Cl prepulse) after addition of apical Na+. Ethylisopropylamiloride inhibits Na(+)-dependent pHi recovery at micromolar concentrations. PTH leads to an inhibition of apical Na+/H+ exchange activity; inhibition is observed even at a concentration of 5 pM PTH. PTH given at maximally effective concentrations (24 nM) reduces the total Na+/H+ exchange capacity by 60%-70%. Apical as well as basolateral hormone additions elicit an inhibitory response at low (5 pM) or high (24 nM) concentrations. Forskolin (activation of protein kinase A) and phorbol esters (activation of protein kinase C) lead to an inhibition of Na+/H+ exchange activity (60%-70% inhibition). These observations suggest that Na+/H+ exchange activity is preferentially located in the apical membranes of OK cells kept in monolayer configuration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parathyroid hormone regulation of Na+/H+ exchange in opossum kidney cells: polarity and mechanisms. 217 44

We investigated cellular mechanisms mediating the parathyroid hormone (PTH)-induced increase in cytosolic free Ca2+ concentration ([Ca2+]i) in isolated perfused rabbit connecting tubules. Prior and/or concomitant exposure to 0.5 mM of N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-8), a cyclic nucleotide-dependent protein kinase inhibitor, abolished the rise in [Ca2+]i produced by 0.1 nM PTH in five connecting tubules and suppressed it by approximately 50% in another five. In the latter, there was a delayed onset in the rise of [Ca2+]i. Such responses contrasted to the prompt increase in [Ca2+]i in PTH-stimulated control tubules. However, when H-8 was withdrawn, [Ca2+]i rose within minutes to reach a plateau value similar to the uninhibited response to PTH in controls, indicating rapidly reversible inhibition by H-8. In an otherwise identical protocol, 0.5 mM H-8 also reversibly suppressed the rise in [Ca2+]i induced by 0.175 mM 8-Br-cAMP. In contrast to the stimulatory effect of 8-Br-cAMP on [Ca2+]i, 1 mM 8-Br-cGMP caused no increase. At a concentration of 0.4 mM, the Rp diastereomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS), a well-characterized cAMP-dependent protein kinase inhibitor, totally abolished the rise in [Ca2+]i caused by 0.1 nM PTH. We conclude that a cAMP-dependent protein kinase plays an important role in the PTH-stimulated rise in [Ca2+]i in the rabbit connecting tubule. Since the increase in [Ca2+]i was shown previously to depend on extracellular Ca2+, we propose that cAMP-dependent protein phosphorylation is important in mediating PTH-stimulated Ca2+ fluxes across plasma membranes of connecting tubule cells.
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PMID:Evidence for cAMP-dependent protein kinase in mediating the parathyroid hormone-stimulated rise in cytosolic free calcium in rabbit connecting tubules. 253 2

The influence of phorbol myristate acetate (PMA), an activator of protein kinase c, on the secretion of parathyroid hormone from collagenase-dispersed bovine parathyroid cells was tested. The cells were incubated at low (0.5 mM) or high (2.0 mM) concentrations of calcium in the medium, and the hormone secreted into the medium was measured by a radioimmunoassay that recognizes both intact and C-terminal fragments of hormone. At low calcium, the secretory rate averaged 32 +/- 3.8 ng.h-1.(10(5) cells)-1. The addition of 1.6 microM PMA did not affect secretion. At high calcium there was a significant suppression of secretion by 38% to 19.8 +/- 3 ng.h-1.(10(5) cells)-1. The addition of 1.6 microM PMA significantly stimulated hormone secretion to 35.8 +/- 8 ng.h-1.(10(5) cells)-1, a rate indistinguishable from low calcium. This stimulatory effect of PMA at high calcium was seen at PMA concentrations as low as 1.6 nM, did not occur with a biologically inactive 4 alpha-isomer of phorbol ester, and was independent of changes in cellular adenosine 3',5'-cyclic monophosphate levels. Examination of 32P-labeled phosphoproteins by two-dimensional gel electrophoresis revealed acidic proteins of approximately 20,000 and 100,000 Da that were phosphorylated at low and high calcium + 1.6 microM PMA but not at high calcium alone. The protein kinase c activity associated with the membrane fraction of parathyroid cells significantly decreased 40% when the cells were incubated at high vs. low calcium. The data suggest that calcium may regulate parathyroid hormone secretion through changes in protein kinase c activity of the membrane fraction of the cell and protein phosphorylation.
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PMID:Effect of phorbol myristate acetate on secretion of parathyroid hormone. 282 13

Studies were made on the mechanism of the effect of parathyroid hormone (PTH) on the activity of (Ca2++Mg2+)-ATPase, a membrane bound Ca2+-extrusion pump enzyme from the basolateral membranes (BLM) of canine kidney (Km for free Ca2+ = 1.3 X 10(-7) M, Vmax = 200 nmol Pi/mg/min). At 1 X 10(-7) M free Ca2+, both PTH (10(-7)-10(-6) M) and cAMP (10(-6)-10(-4) M) stimulated (Ca2++Mg2+)-ATPase activity dose-dependent and their stimulatory effects were inhibited completely by 5 microM H-8, an inhibitor of cAMP-dependent protein kinase. PTH (10(-7) M) also caused 40% increase in 32P incorporation into the BLM and 5 microM H-8 inhibited this increase too. PTH (10(-7) M) was found to stimulate phosphorylation of a protein of Mr 9000 by cAMP dependent protein kinase and 5 microM H-8 was found to block this stimulation also. From these results, it is proposed that PTH stimulates (Ca2++Mg2+)-ATPase activity by enhancing its affinity for free Ca2+ via cAMP-dependent phosphorylation of a BLM protein of Mr 9000.
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PMID:Increase of (Ca2++Mg2+)-ATPase activity of renal basolateral membrane by parathyroid hormone via cyclic AMP-dependent membrane phosphorylation. 282 70

Dispersed chick adrenocortical cells were incubated with avian parathyroid hormone (aPTH) or ACTH. Accumulation of cyclic AMP (cAMP), activity of cAMP-dependent protein kinase and the secretion of corticosterone and aldosterone, in response to these hormones, were measured. Accumulation of cAMP and activity of cAMP-dependent protein kinase were stimulated by both aPTH and ACTH as well as by cholera toxin. Cyclic AMP production followed a similar time-course when stimulated by either peptide hormone. Stimulation of steroid hormone secretion was detectable after 20 min of incubation with ACTH, but only after 40 min with aPTH. The maximal steroid hormone secretion by adrenocortical cells was similar when induced by either peptide hormone. The aPTH concentrations needed for half-maximal response of corticosterone and aldosterone secretion were higher than those for ACTH (2.5- and 2-fold respectively), but still within the physiological range. The 11 beta-hydroxylase inhibitor metyrapone inhibited the secretion of both corticosterone and aldosterone when induced by either aPTH or ACTH. The results suggest that aPTH is almost as potent as ACTH in stimulating the secretion of corticosterone and aldosterone from chick adrenocortical cells and utilizes a cAMP-dependent pathway similar to that of ACTH.
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PMID:Stimulation of chick adrenal steroidogenesis by avian parathyroid hormone. 282 8

We studied the effects of the (Sp) and (Rp) diastereomers of the phosphorothioate analogue of cyclic AMP (cAMPS) on the excretion of electrolytes in the isolated perfused rat kidney. cAMPS is highly permeant across the peritubular cell membrane and is not metabolized by the rat kidney (Coulson et al., Life Sci. 32: 1489-1498, 1983). Addition of 10 microM cAMPS(Sp) to the perfusate resulted in a significant phosphaturia, bicarbonaturia, magnesuria and natriuresis and no change in renal vascular resistance or glomerular filtration rate. Fractional excretion of calcium was elevated by cAMPS(Sp) but proportionately less than the fractional excretion of sodium so that the ratio of calcium to sodium clearances was significantly lowered. cAMPS(Rp) 10 or 100 microM was without effect on renal electrolyte excretion. The parathyroid hormone-like effects of the (Sp) diastereomer are consistent with its known ability to activate protein kinase.
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PMID:Effects of (Sp)- and (Rp)-adenosine cyclic 3',5'-phosphorothioates on electrolyte excretion by the isolated perfused rat kidney. 298 44

Pretreatment with 10(-8) M retinoic acid for 4 days caused changes in three distinct components of the parathyroid hormone (PTH)-stimulated cyclic adenosine 3':5'-monophosphate response in a clonal rat osteogenic sarcoma cell line, UMR 106-06: the amplitude of the cyclic adenosine 3':5'-monophosphate response to PTH was moderately increased after pretreatment with retinoic acid; while the cellular content of the two isoenzymes of the cyclic adenosine 3':5'-monophosphate-dependent protein kinase was approximately equal in control cells, retinoic acid pretreatment was associated with a marked increase in the ratio of type II to type I holoenzyme activity. This change might be due to a decrease in the type I holoenzyme as suggested by immunofluorescence detection of decreased type I regulatory subunit in fixed cells together with the relative decrease in type I holoenzyme determined biochemically; there was a marked alteration of the pattern of PTH-stimulated protein kinase isoenzyme activation from predominantly type I isoenzyme in control cells to almost exclusively type II isoenzyme in retinoic acid-treated cells. Growth inhibition by submaximal amounts of PTH and retinoic acid when added together was greater than that for either agent alone.
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PMID:Effect of retinoic acid on cellular content and human parathyroid hormone activation of cyclic adenosine 3':5'-monophosphate-dependent protein kinase isoenzymes in clonal rat osteogenic sarcoma cells. 299 62

It is known that parathyroidectomy, administration of parathyroid hormone (PTH), and dietary phosphate depletion or excess result in variations in phosphaturia and in phosphate transport through brush border membrane vesicles isolated from the kidneys of various animals. Parathyroid hormone has been shown to ultimately phosphorylate some brush border membrane proteins and it has been postulated that the resulting phosphaturia is related to this phosphorylation. However, it is not known whether the regulation of phosphate transport by the diet is affected through similar pathways. Our experiments were designed to study the phosphorylation of brush border membrane with [gamma-32P]ATP using the intrinsic protein kinase of the membranes. Five groups of rats were used: normal, phosphate loaded, phosphate depleted, and thyroparathyroidectomized and acutely loaded with parathyroid hormone. In each series of animals, the proteins whose phosphorylation was cAMP dependent were detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis, and their phosphorylation with various concentrations of ATP, in the presence or absence of cAMP in the incubation medium, was quantified. In the normal rat, 17 proteins were phosphorylated, the phosphorylation of two of them (Mr, 71 000 and 84 000) being cAMP dependent. Maximal response to cAMP for these two proteins was obtained with 10 microM cAMP. The peaks of phosphorylation were observed at pH 7 for protein 71 000 and pH 10 for protein 84 000. When brush border membranes from normal rats were incubated with 10-100 microM ATP, cAMP-dependent phosphorylation increased to reach a maximal phosphorylation of 4.44 +/- 0.90 pmol/mg protein for protein 71 000 and 1.32 +/- 0.15 pmol/mg protein for protein 84 000.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal brush border membrane phosphorylation: influence of pH, cAMP and ATP concentrations, parathyroid hormone status, and dietary phosphate. 300 May 57

The capacity of parathyroid hormone (PTH) to stimulate the renal production of 1,25-dihydroxyvitamin D declines with age. Since the action of PTH in the kidney is mediated by cAMP, we have examined the effect of PTH and forskolin on renal cortical adenylate cyclase in young (3 months), adult (13-15 months), and old (25-27 months) F344 rats. PTH-dependent adenylate cyclase, measured as cAMP accumulation in cortical slices, was reduced in adult and old rats compared to young rats over a PTH concentration range of 0.015-15 units/ml. There was no difference in PTH-dependent adenylate cyclase activity between adult and old rats. Renal plasma membrane preparations demonstrated similar changes in PTH-stimulated adenylate cyclase activity. There was no difference in calcitonin, forskolin, or guanyl-5-ylimidodiphosphate (Gpp(NH)p) stimulation of adenylate cyclase in plasma membranes from each age group, suggesting that the defect lies in the membrane receptor for PTH. The decreased adult sensitivity to PTH could be reversed by thyroparathyroidectomy. PTH stimulation of cytosolic protein kinase activity did not change with age. These results suggest that the decrease in PTH-dependent adenylate cyclase is due to the alterations at the level of PTH receptor. These alterations may be in response to the increase in serum PTH seen in these animals with increasing age.
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PMID:Effect of age on parathyroid hormone and forskolin stimulated adenylate cyclase and protein kinase activity in the renal cortex. 303 Jul 93


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