Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sequestration of calcium into an intracellular storage site is an important mechanism in helping to maintain a low cytoplasmic Ca2+ level in many cells. In platelets, increasing cytoplasmic cAMP lowers the free calcium level in correlation with the phosphorylation of a 22 kD protein. This protein has been thought to enhance uptake of calcium into a platelet membrane bound storage site by activating a calcium-ATPase activity by analogy with phospholamban in cardiac muscle. The evidence for an analogue of phospholamban in platelets is unclear. A pathway involving cAMP dependent kinase also seems unlikely to account for the transience of the calcium signal following agonists in platelets, some of which inhibit the cAMP dependent kinase. Here we discuss the issue of whether activation of protein kinase C, which follows agonist action, leads to enhanced calcium sequestration in platelets and if so, what indications there are for a mechanism. The evidence from our experiments with phorbol myristate acetate treated platelets shows that such an enhancement can be produced by activating protein kinase C. Phosphorylation studies suggest the involvement of a polypeptide or polypeptides distinct from the 22 kD polypeptide. Further work to test this idea is necessary. A brief overview of research on the role of phosphoproteins in calcium regulation in platelets and comparison with their role in cardiac muscle is also presented.
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PMID:Calcium sequestration in human platelets: is it stimulated by protein kinase C? 267 Feb 38

Kaempferol, 3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one, was found to inhibit bovine aorta myosin light chain kinase with a Ki of 0.3-0.5 microM. It was found to be competitive with ATP and non-competitive with isolated myosin light chains. The specificity of this inhibitor was studied relative to protein kinase C and cAMP dependent protein kinase (IC50 = 15 microM and 150 microM, respectively). It appears not to interact strongly with calmodulin binding proteins, such as Ca2+-calmodulin dependent phosphodiesterase (IC50 = 45 microM), and had little effect on actin-activated myosin subfragment-1 ATPase activity (IC50 greater than 100 microM) or smooth muscle phosphatase activities (IC50 greater than 100 microM).
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PMID:Kaempferol inhibits myosin light chain kinase. 280 9

Several newly synthesized 4-hydroxycinnamamide derivatives such as 3-(3',5'-di-isopropyl-4'-hydroxybenzylidene)-2-oxindol (ST 280), 3-(3',5'-di-methylthiomethyl-4'-hydroxybenzylidene)-2-oxindole (ST 458), alpha-cyano-3-ethoxy-4-hydroxy-5-phenylthiomethylcinnamamide (ST 638) and 3-(3'-ethoxy-4'-hydroxy-5'-phenylthiomethylbenzylidene)-2-pyrol idinone (ST 642) were found to inhibit tyrosine-specific protein kinase activity of the epidermal growth factor (EGF) receptor with IC50 values of 0.44 microM, 0.44 microM, 0.37 microM and 0.85 microM, respectively. None of them showed inhibitory effect on the enzyme activities of serine- and/or threonine-specific protein kinases such as cAMP-dependent protein kinase, Ca2+/phospholipid-dependent protein kinase C, casein kinase I and casein kinase II. In addition, none of them had effect on Na+/K+-ATPase or 5'-nucleotidase. The results suggest that the compound ST 280, ST 458, ST 638 and ST 642 are potent and specific inhibitors of tyrosine-specific protein kinase.
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PMID:Specific inhibitors of tyrosine-specific protein kinase, synthetic 4-hydroxycinnamamide derivatives. 282 Mar 97

The inhibitory effects of Ca2+-binding proteins on tyrosine phosphorylation of p36 protein isolated from bovine intestinal epithelium by immunoprecipitated p130fps were investigated. S-100 protein dose dependently inhibited the p36 phosphorylation, and calmodulin weakly depressed the phosphorylation, whereas parvalbumin and troponin C had no significant effects. The S-100 preparation purified from bovine brain did not contain phosphatase activity or ATPase activity. The concentration of ATP did not affect the S-100-mediated inhibition of phosphorylation but the substrate protein, p36, reversed the inhibition. S-100 similarly inhibited the tyrosine phosphorylation of p36 by p60src but did not affect the p36 phosphorylation by protein kinase C. S-100 inhibited the tyrosine kinase activity of p130fps using the other substrates tested as well. These results suggest that S-100 interacts with the substrate binding site of retroviral tyrosine-specific protein kinases and may play a regulatory role in the tyrosine phosphorylation.
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PMID:Modulation of tyrosine phosphorylation of p36 and other substrates by the S-100 protein. 283 78

The activity of the Na,K-ATPase can be sensitive to physiological changes in Cai. Intracellular proteins such as calnaktin, calmodulin, and protein kinase C could regulate the pump during transient changes in Cai. The mechanisms by which these proteins interact with the Na,K-ATPase, their distribution in different kinds of cells, and their role in regulating the Na,K-ATPase are not yet determined. Preliminary data indicate that an increase in Cai within the physiological range could be associated with either a stimulation or an inhibition of enzyme activity or a change in the affinity of the Na,K-ATPase for ouabain. The type of response probably depends on the kind of cell, its associated intracellular proteins, and its physiological state. Ca and intracellular proteins could play a key role in the regulation of the Na,K-ATPase by hormones.
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PMID:Modulation of the Na,K-ATPase by Ca and intracellular proteins. 283 35

Six weeks after induction of diabetes, the rate of ouabain-sensitive 86Rb+ accumulation, a parameter which reflects Na+ + K+-ATPase pumping activity, was significantly reduced in endoneurial preparations of sciatic nerve from untreated diabetic rats compared with that in control rats (Trial, 1, 0.19 +/- 0.09 versus 0.48 +/- 0.13 pmol/min per mg wet weight of tissue, p less than 0.001; Trial 2, 0.27 +/- 0.16 versus 0.47 +/- 0.18, p less than 0.01). This decrease in ouabain-sensitive 86Rb+ uptake was not observed in nerves from diabetic rats maintained on sorbinil (an aldose reductase inhibitor) or myo-inositol diets. Protein kinase C activity was demonstrated in the soluble fraction of a sciatic nerve homogenate by assaying for lipid-activated, Ca+-dependent phosphorylation of calf thymus histone. No significant difference in the time course of kinase C activity was observed between cytosol fractions of nerve homogenates from control and diabetic rats (control, 6.22 +/- 0.97 pmol 32P incorporated/mg cytosol protein in 50 min; diabetic, 5.32 +/- 0.71). Three low molecular weight neural proteins (each with Mr less than 29,000) were identified as substrates for protein kinase C.
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PMID:Reduced Na+ + K+-ATPase activity in peripheral nerve of streptozotocin-diabetic rats: a role for protein kinase C? 284 Mar 14

The binding of interleukin 2 (IL 2) to specific cell surface receptors provides a unique proliferative stimulus to sensitive T-lymphocytes. The purpose of this investigation was to examine the hypothesis that IL 2 stimulus-response coupling in the IL 2-dependent murine T-lymphocyte clone CTLL-2 employed some of the intracellular second messengers used by other growth factors. No evidence was obtained to implicate changes in intracellular Ca2+ concentrations, protein kinase C activation, or stimulation of the Na+/H+ antiporter or the Na+/K+ ATPase as requirements for stimulation by recombinant human IL 2. Pertussis toxin did not inhibit IL 2-driven growth of CTLL-2, and while cholera toxin did inhibit growth, its effect was optimal 6 to 8 hr after addition of IL 2 and could be mimicked by increased intracellular cyclic-AMP. Thus, guanine nucleotide-binding regulatory proteins do not appear to be involved in stimulation by this lymphokine. Together, these data suggest that IL 2 may not use any of the same types of intracellular second messengers generated subsequent to the binding of antigen or mitogen by T-lymphocytes.
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PMID:Does interleukin 2 stimulus-response coupling result in generation of intracellular second messengers? 284 44

The anticancer ether lipid analogs ET-18-OCH3 and BM 41.440 inhibited Na, K-ATPase in the purified rat brain membrane fragments, with a potency comparable to that of their inhibition of protein kinase C. They also inhibited Na,K-ATPase in the crude membrane fraction of HL60 cells. Kinetic analysis indicated that the lipids had a mode of action different from that of ouabain, a classic inhibitor of the ATPase. The lipids also blocked 22Na uptake in the inside-out membrane vesicles of human erythrocytes. It is suggested that Na,K-ATPase might represent an additional site with which certain protein kinase C inhibitors can interact to alter cellular activities.
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PMID:Inhibition of Na,K-ATPase and sodium pump by anticancer ether lipids and protein kinase C inhibitors ET-18-OCH3 and BM 41.440. 284 26

Five protein kinases are shown to serve as specific phosphatases in the absence of ADP. Although the rates of hydrolysis are very slow compared to the forward phosphorylation rates under optimal conditions, they are of the same order as the reverse reaction in the presence of ADP. Because cells contain approximately equal to 3 mM ATP, neither the reverse reaction nor the phosphatase is likely to play a physiological role. beta-casein B phosphorylated by the catalytic subunit of cAMP-dependent protein kinase (protein kinase A) is specifically dephosphorylated by protein kinase A but not by polypeptide-dependent protein kinase (protein kinase P). beta-casein B phosphorylated by protein kinase P is specifically dephosphorylated by protein kinase P but not by protein kinase A. Histone H1 phosphorylated by protein kinase C is dephosphorylated by the same enzyme in the absence of ADP. In all cases tested addition of ADP and F1-ATPase accelerates moderately the rate of dephosphorylation. Native H+-ATPase from yeast plasma membranes is isolated mainly in the phosphorylated form. It is dephosphorylated and rephosphorylated by protein kinase P but not by protein kinase A. Protein-tyrosine kinase of the epidermal growth factor receptor phosphorylates the random synthetic polypeptide poly(Glu80Tyr20). The phosphorylated polymer is specifically dephosphorylated in the absence of ADP by epidermal growth factor receptor preparations but not by insulin receptor preparations. The same polymer phosphorylated by insulin receptor is dephosphorylated by insulin receptor but not by epidermal growth factor receptor preparations. By using a cycle of dephosphorylation-rephosphorylation, it is possible to identify proteins that are phosphorylated by these protein kinases in vivo. Should this method be applicable to additional protein kinases, it should be possible to estimate the quantitative contribution of each protein kinase to a single phosphoprotein.
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PMID:Specific dephosphorylation of phosphoproteins by protein-serine and -tyrosine kinases. 290 Oct 92

The effects of the alpha 1-adrenergic agonist phenylephrine (PE) and the phorbol ester 4 beta-phorbolmyristate-acetate (PMA) on sodium pump function were studied in the rat liver. In order to distinguish between direct and indirect influences, ouabain-sensitive 86Rb uptake by intact liver slices was compared with ouabain-sensitive Na+/K+-ATPase activity in plasma membranes isolated from PE and PMA-perfused livers. At a buffer Ca2+ level of 2.5 mmol/l, PE (10 mumol/l) caused an initial stimulation of both 86Rb uptake and Na+/K+-ATPase activity followed at 5 min by a decrease in both activities. Both actions were blocked by the alpha 1-antagonist prazosin. The decrease in ouabain-sensitive Na+/K+-ATPase was paralleled by an increase in Mg2+ ATPase activity. At a Ca2+ level of 1.5 mmol/l, PE stimulation of 86Rb uptake and Na+/K+-ATPase was sustained, and the inhibitory component was not expressed. PMA (4 mumol/l) reduced 86Rb uptake and Na+/K+-ATPase and similar to PE, this inhibition was paralleled by an increase of Mg2+-ATPase activity. 4 alpha-PMA, which does not activate protein kinase C, failed to influence 86Rb uptake or Na+/K+-ATPase. These results demonstrate that PE and PMA effects on ouabain-sensitive 86Rb uptake are preserved in isolated membranes, indicating a direct influence on the Na+/K+-ATPase. A role for protein kinase C in modulating sodium pump activity is suggested.
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PMID:Influence of alpha 1-adrenergic receptor stimulation and phorbol esters on hepatic Na+/K+-ATPase activity. 290 84


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