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)

The effect of parathyroid hormone and calcitonin on the renal excretion of phosphate, calcium, and cyclic AMP was evaluated in the thyroparathyroidectomized hamster, a mammal apparently reisstant to the phosphaturic effect of parathyroid hormone. Parathyroid hormone did not increase phosphate excretion, although it decreased excretion of calcium and increased urinary excretion of cyclic AMP. This lack of a phosphaturic response to parathyroid hormone was not reversed by administration of 25-OH vitamin D or infusions of calcium or phosphate. Calcitonin, another potentially phosphaturic hormone, also vailed to increase phosphate excretion but markedly elevated urinary excretion of cyclic AMP. In hamsters pretreated with infusion of urinary ammonium chloride, which decreased plasma and urinary pH, both parathyroid hormone and calcitonin increased excretion of phosphate as well as that of cyclic AMP. Acetazolamide had no phosphaturic effect in ammonium chloride-loaded hamsters, and it decreased cyclic AMP and calcium excretion. Alkalinization of urine by acetazolamide did not prevent the phosphaturic effect of parathyroid hormone in ammonium chloride-loaded hamsters, but it blocked the increase in urinary cyclic AMP excretion. Parathyroid hormone and calcitonin both stimulated adenylate cyclase in a cell-free system (600-g pellet) from hamster renal cortex, elevated tissue cyclic AMP levels, and activated protein kinase in tissue slices from hamster renal cortex. In acid medium, the increase in cyclic AMP and activation of protein kinase in response to parathyroid hormone was diminished, but addition of acetazolamide restored responsiveness of both parameters to control values. Acetazolamide, on the other hand, did not influence adenylate cyclase or its response to parathyroid hormone or cyclic AMP phosphodiesterase activity. We conclude that the lack of a phosphaturic effect of parathyroid hormone and calcitonin in the hamster depends on steps in the cellular action of these hormones, steps that are sensitive to pH subsequent to cyclic AMP generation and protein kinase activation. In addition, acetazolamide may potentiate the phosphaturic effect of parathyroid hormone by promoting accumulation of cyclic AMP in tissue. Thus, the hamster is a particularly useful model for studies of syndromes in which there is renal resistance to phosphaturic hormones.
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PMID:Mechanism of resistance to the phosphaturic effect of the parathyroid hormone in the hamster. 1 74

Parathyroid hormone (PTH) was infused into thyroparathyroidectomized rats, and the protein kinase activity of the kidney was studied. When the tissue was homogenized in a buffer containing 5 mM potassium phosphate (pH 7.0), 2 mM EDTA, 1 mM mercaptoethanol, and 5 mM theophylline, the total protein kinase activity (measured in the presence of 5 muM cAMP) in the cytosol was decreased by the infusion of PTH, exhibiting an inverse relationship to cAMP level in the renal tissue. The decrease of total activity was accounted for by a decrease of cAMP-dependent kinase activity, and such a change was induced also by the infusion of calcitonin or dibutyryl cAMP. A substantial enzyme activity was solubilized from the particulate fraction with a buffer containing KC1. The infusion of PTH increased the kinase activity (activities measured in both the presence and absence of cAMP) solubilized from the particulate fraction, suggesting the translocation of activated enzyme from cytosol to some particulate cell component(s). However, when KC1 was added to the homogenization buffer in concentrations up to 150 mM or even higher, the total protein kianse activities in the cytosols of control and PTH rats were similar and there was simply an increase in the fraction of cAMP -independent activity. These observations indicate that the hormonally-induced increase of cAMP in vivo activates protein kinase of the kidney, and the activation of kinase results in apparent translocation of the enzyme from the soluble to the particulate fraction when the tissue is homogenized in buffers of low ionic strength. The physiological significance of this phenomenon, however, cannot be evaluated, due to the fact that the increased association of activated kinase with particulate component(s) is reversed by employing a homogenization buffer containing what is probably a physiological concentration of salt.
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PMID:Effects of parathyroid hormone in vivo on the protein kinase activity in rat kidney. 17 95

Parathyroid hormone (PTH) and glucagon increase the urinary fractional excretion of phosphate, but insulin administration is associated with a decreased fractional excretion of phosphate. It was the purpose of this study to determine whether insulin will antagonize the effects of PTH and glucagon on cAMP levels and protein kinase activation of rat renal cortex. In situ incubation studies were performed on rat renal cortical slices exposed to insulin, PTH, and glucagon. Insulin alone did not affect the tissue cAMP and cGMP levels or the state of protein kinase activation. Preincubation of slices with insulin, however, did significantly inhibit increases in protein kinase activation induced by both PTH and glucagon. Insulin also significantly inhibited PTH-stimulated increases in tissue cAMP levels, but did not blunt the elevations of cAMP levels induced by glucagon. Insulin (10(-9) M) had no effect on either the in vitro activity of adenylate cyclase, basal or PTH-stimulated, or on the activities of low Km cytosolic or membrane-bound cAMP phosphodiesterase. The data show that insulin antagonizes activation of protein kinase by both PTH and glucagon in renal cortex. Separate mechanisms are probably involved for PTH and glucagon interaction. The antiphosphaturic effect of insulin in vivo may result in part from this antagonism at the cellular level.
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PMID:Insulin inhibition of hormone-stimulated protein kinase systems of rat renal cortex. 22 Aug 84

Parathyroid hormone action on renal proximal tubule function involves phospholipase C/protein kinase C as well as adenylate cyclase/protein kinase A mediated regulatory pathways. Tissue culture experiments suggest that low concentrations of PTH affect preferentially the phospholipase C/protein kinase C pathway. In vivo, both regulatory cascades are probably involved in the regulation of proximal tubule function. It is not clear at present whether the two intracellular pathways are linked to one or two PTH receptors. A polarized distribution of PTH receptor(s) involving different second messengers appears possible in proximal tubule epithelial cells. High-affinity (Kd 10(-11)-10(-12) M) PTH receptors in the range of circulating PTH concentrations in vivo remain to be identified. Structural and functional characterization of PTH receptors as well as of the PTH-sensitive intracellular mediators and transport systems form the basis for a better understanding of PTH-dependent regulation of proximal tubule function.
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PMID:Parathyroid hormone receptors in control of proximal tubule function. 131 47

Parathyroid hormone (PTH) has been shown to induce osteoblastic activity via a complex signal transduction process which is mediated either by cAMP or cytosolic calcium ([Ca2+]i), or a combination thereof. One of the PTH functions in osteoblasts is the induction of ornithine decarboxylase (ODC) activity. We have analyzed the second messengers involved in this process. 8-Bromo cAMP, a cAMP derivative, enhanced ODC activity in UMR106-01 osteoblastic cell system. The calcium ionophore A23187 and the protein kinase stimulator phorbol-12-myristate 13-acetate did not alter ODC activity. ODC activity was increased by bPTH-(1-34), PGE1, and PGE2 which stimulated both cAMP and [Ca2+]i. In contrast, PTH-(2-34), propionyl bPTH-(2-34), bPTH-(3-34), bPTH-(7-34), and PGF2 alpha, which only enhanced [Ca2+]i but not cAMP, had no effect on ODC activity. Thus, the stimulation of ODC in UMR106 cells by PTH appeared to be mediated primarily via the cAMP signal transduction pathway, and the mere increase in intracellular calcium could not account for the stimulation of ODC activity. ODC mRNA level was found to be increased by PTH treatment. Therefore, translation of ODC may be stimulated by PTH. Moreover, PTH also stimulated ODC antizyme activity, suggesting that the ODC degradation rate was increased.
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PMID:Regulation of ornithine decarboxylase by parathyroid hormone in osteoblastic cell systems. 133 75

Parathyroid hormone (PTH) in opossum kidney (OK) cells leads to inhibition of Na-Pi cotransport, to the generation of inositol trisphosphate (IP3) and adenosine 3',5'-cyclic monophosphate (cAMP) and to a phosphorylation of proteins present in an enriched apical membrane fraction (27, 28; for review see Ref. 23). In the present report we have identified two of these phosphoproteins with molecular weights of approximately 22,000 and approximately 24,000, respectively, as guanosine 5'-triphosphate (GTP)-binding proteins, ADP-ribosylated by the Clostridium botulinum exotoxin C3 and recognized by an anti-rho polyclonal antibody but not by pan-ras monoclonal antibody; as suggested by Western-blot analysis the content of the proteins recognized by the anti-rho antibody did not alter in the membrane fraction as a function of treatment with PTH. Transient permeabilization of OK cells using streptolysin O and including the C3 exotoxin attenuated PTH-dependent inhibition of Na-Pi cotransport at hormone concentrations higher than 10(-10) M; residual PTH-dependent inhibition is equal to that observed after pharmacological activation of protein kinase A and protein kinase C, respectively. C3 exotoxin did not alter PTH-dependent generation of cAMP but modified production of IP3; it was increased at 10(-11) M and reduced at 10(-8) M PTH, respectively. It is suggested that protein kinase A may be involved in the phosphorylation of C3 exotoxin-sensitive G proteins (rho/rac). These proteins could be involved in PTH signal transduction.
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PMID:Involvement of C3 exotoxin-sensitive G proteins (rho/rac) in PTH signal transduction in OK cells. 156 70

Phosphate uptake by proximal renal cells derived from the human kidney occurs by a saturable process that is approximately 85% dependent on the presence of sodium. Kinetic analysis is consistent with two distinct transport events with Km of 0.08 and 0.63 mM and Vmax of 3.4 and 11.0 nmol.mg-1.3 min-1, respectively. Parathyroid hormone (PTH), isoproterenol, and prostaglandin E2 (PGE2) increased cellular adenosine 3',5'-cyclic monophosphate (cAMP). PTH-stimulated cAMP prevented binding of the photolabel 8-azido[32P]cAMP with a half-maximal effective concentration (EC50) of 1 nM PTH, 30-fold lower than the EC50 for intracellular cAMP accumulation. These data are qualitatively similar to those observed in OK cells. PTH did not inhibit phosphate uptake in human cells, although it activated cAMP-dependent protein kinase and increased cytosolic calcium. Thus phosphate uptake in human proximal renal cells maintained in short-term culture is unresponsive to PTH in spite of increased cytosolic calcium and activation of the cAMP pathway.
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PMID:Protein kinase A, cytosolic calcium, and phosphate uptake in human proximal renal cells. 247 35

Parathyroid hormone (PTH) inhibits sodium/phosphate (Na+/Pi) cotransport across the apical membrane of opossum kidney (OK) cells principally through two pathways. First, cAMP stimulation and activation of protein kinase A; second, diacylglycerol release and stimulation of protein kinase C. Studies were designed to determine the importance of these regulatory cascades. Down-regulation of protein kinase C with prolonged phorbol ester (12-O-tetradecanoylphorbol 13-acetate (TPA] treatment leads to a refractory state in which the cells do not respond to PTH (10(-8) M), cAMP (10(-4) M) or rechallenge of TPA (200 nM) even though Na+/Pi cotransport is similar to control cells (8.1 +/- 0.1 nmol.mg-1 protein.5 min-1). Staurosporine, an inhibitor of protein kinase C, resulted in the complete inhibition of PTH, cAMP and TPA action in a dose-dependent manner. PTH, cAMP and TPA were additive below maximal concentrations, but had no further effect at maximal agonist concentrations. These results suggest that protein kinase C activity is important in PTH-mediated inhibition of Na+/phosphate cotransport in OK cells.
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PMID:Parathyroid hormone inhibition of Na+/phosphate cotransport in OK cells: requirement of protein kinase C-dependent pathway. 254 12

The kidney is the principal physiologic site of production of biologically active 1,25-dihydroxyvitamin D. The 25-hydroxyvitamin D-1 alpha-hydroxylase (1-OHase) activity found in renal mitochondria is under tight hormonal control. Parathyroid hormone stimulates the renal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D in young animals, which is accompanied by dephosphorylation of ferredoxin (Fx), a component of the mitochondrial 1-OHase enzyme complex (Siegel, N., Wongsurawat, N., and Armbrecht, H. J. (1986) J. Biol. Chem. 261, 16998-17003). The present study investigates the capacity of Fx to be phosphorylated in vitro and to modulate the 1-OHase activity of a reconstituted system. Fx was phosphorylated by renal mitochondrial type II protein kinase. Phosphorylation did not alter Fx mobility on sodium dodecyl sulfate gels but did decrease the pI as measured by isoelectric focusing. Amino acid analysis demonstrated that 1 mol of serine and 1 mol of threonine were phosphorylated per mol of Fx. Peptide mapping of phosphorylated Fx was consistent with phosphorylation of serine 88 and threonine 85 or 97. Fx was selectively dephosphorylated by rabbit skeletal muscle protein phosphatase C2 but not C1. Phosphorylation of Fx significantly inhibited the 1-OHase activity of a reconstituted system consisting of Fx reductase, Fx, and renal mitochondrial cytochrome P-450. These findings suggest that phosphorylation/dephosphorylation of Fx may play a role in modulating renal 1,25-dihydroxyvitamin D production.
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PMID:Phosphorylation of ferredoxin and regulation of renal mitochondrial 25-hydroxyvitamin D-1 alpha-hydroxylase activity in vitro. 276 68

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


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