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

Isopeptides of the endothelin gene family, including sarafotoxin, caused a concentration-dependent increase in intracellular-free calcium (cytosolic calcium) in cultured human and rat glomerular mesangial cells. The calcium increments had two components, a spike increment resulting from mobilization of intracellular calcium and a sustained calcium increment as a result of endothelin activation of calcium influx. ET-dependent calcium influx occurred through dihydropyridine-insensitive calcium channels which were blocked by NiCl and allowed entry of Mn2+. In human mesangial cells, ET stimulated periodic oscillations of cytosolic Ca2+ that reflect synchronous signalling in localized populations. Calcium signalling evoked by the ET isopeptides showed cross-desensitization among the four ET-peptides tested. Although protein kinase C activation acutely reduced ET-induced calcium signalling, the desensitization by ET isopeptides was independent of protein kinase C. If ET was added to cells incubated with an inhibitor of the endoplasmic reticulum calcium ATPase, it became apparent that ET activated a calcium efflux pathway which reduced cytosolic calcium. These data, therefore, demonstrate that calcium signalling is a common response in both human and rat cultured mesangial cells incubated with different ET isopeptides.
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PMID:The effects of endothelin on cytosolic calcium in cultured human and rat glomerular mesangial cells. 166 3

Jurkat and MOLT-4 cultured T lymphoblasts were loaded with low concentrations (30-50 microM) of indo-1 and with high concentrations (3.5-4.5 mM) of quin-2, respectively, in order to follow the activation of calcium transport pathways after stimulation of the cells by a monoclonal antibody against the T cell antigen receptor (aCD3), or after the addition of thapsigargin, a presumed inhibitor of endoplasmic reticulum calcium pump. In the indo-1 loaded cells the dynamics of the intracellular calcium release and the calcium influx could be studied, while in the quin-2 overloaded cells the changes in cytoplasmic free calcium concentration ([Ca2+]i) were strongly buffered and the rate of calcium influx could be quantitatively determined. We found that in Jurkat lymphoblasts, in the absence of external calcium, both aCD3 and thapsigargin induced a rapid calcium release from internal stores, while upon the readdition of external calcium an increased rate of calcium influx could be observed in both cases. aCD3 and thapsigargin released calcium from the same intracellular pools. The calcium influx induced by either agent was of similar magnitude and had a nonadditive character if the two agents were applied simultaneously. As demonstrated in quin-2 overloaded cells, a significant initial rise in [Ca2+]i or a pronounced depletion of internal calcium pools was not required to obtain a rapid calcium influx. The activation of protein kinase C by phorbol ester abolished the internal calcium release and the calcium influx induced by aCD3, while having only a small effect on these phenomena when evoked by thapsigargin. Membrane depolarization by gramicidin inhibited the rapid calcium influx in both aCD3- and thapsigargin-treated cells, although it did not affect the internal calcium release produced by either agent. In MOLT-4 cells, which have no functioning antigen receptors, aCD3 was ineffective in inducing a calcium signal, while thapsigargin produced similar internal calcium release and external calcium influx to those observed in Jurkat cells.
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PMID:Calcium influx and intracellular calcium release in anti-CD3 antibody-stimulated and thapsigargin-treated human T lymphoblasts. 172 5

Calcium-mobilizing receptors function to regulate ion channels located not only in the plasma membrane but also across the membranes of intracellular organelles, particularly the endoplasmic reticulum. A characteristic feature of such receptors is that they stimulate the hydrolysis of an inositol lipid to generate a pair of second messengers. Diacylglycerol remains within the plasma membrane where it activates protein kinase C leading to the phosphorylation of proteins some of which may regulate specific ionic channels, such as the calcium-dependent potassium channel or the Na+/H+ exchanger which regulates intracellular pH. The inositol trisphosphate (Ins 1,4,5P3) released to the cytosol functions as a second messenger to release calcium from the endoplasmic reticulum. The Ins 1,4,5P3 acts on a specific receptor to enhance the passive efflux of calcium while having no effect on the active calcium pump. There are indications that this Ins 1,4,5P3-induced release of calcium from an internal membrane store might provide an explanation of excitation-contraction coupling in skeletal muscle. Skinned skeletal muscle cells can be induced to contract by adding Ins 1,4,5P3. Mobilization of calcium from intracellular reservoirs by Ins 1,4,5P3 may thus prove to be a ubiquitous and fundamental mechanism for regulating cellular activity.
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PMID:Regulation of ion channels by inositol trisphosphate and diacylglycerol. 242 4

The underlying mechanism of Ca2+ uptake function of cardiac sarcoplasmic reticulum (SR) was investigated in the rat septic shock model produced by cecal ligation and puncture (CLP). The results are as follows. During the early phase of sepsis, the initial rate of ATP-dependent Ca2+ uptake by SR was decreased, while both the capacity of Ca2+ uptake and the activity of Ca(2+)-ATPase were unaffected. In the late sepsis, the impairment in SR function was even greater as the initial rate and the capacity of Ca2+ uptake by SR were significantly decreased, and this was paralleled by a reduction in Ca(2+)-ATPase activity. Although Ca2+ affinity (Km value) to calcium pump and the A0.5 values for Mg2+ and ATP activation on the Ca2+ uptake rate were unchanged, during sepsis the phosphorylation of SR vesicles by adding of catalytic subunit of the cAMP-dependent protein kinase (PKA), calmodulin, or the fragment of PKC into Ca2+ uptake buffer, failed to stimulate Ca2+ uptake activities of SR isolated from early or late septic rats. These data suggest that depression of cardiac SR function is aggravated as sepsis develops, the impairment of SR Ca2+ uptake is possibly based on a mechanism of defective phosphorylation of SR rather than the ionic and energic regulatory actions of Ca2+, Mg2+, ATP on cardiac SR.
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PMID:[Impaired calcium uptake by cardiac sarcoplasmic reticulum and its underlying mechanism during rat septic shock]. 748 74

The effect of protein kinase C on potassium channels in cultured endothelial cells was investigated by using whole-cell patch-clamp techniques. Activation of protein kinase C by phorbol 12-myristate 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDBu), but not phorbol 12-monomyristate (PMM), an inactive analogue of phorbol esters, depressed an outward calcium-dependent potassium current. The inhibitory actions of PMA and PDBu could be reversed by the kinase inhibitor H-7. Cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum calcium pump, and LP-805, a novel vasodilator which also releases endothelium-derived relaxing factors, activated the outward calcium-dependent potassium conductance. PMA and PDBu, but not PMM, reduced the outward conductance induced by cyclopiazonic acid and LP-805. These effects of PMA and PDBu on potassium currents may be mediated either by phosphorylation of ion channels, or by decreasing intracellular calcium concentration.
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PMID:Activation of protein kinase C inhibits potassium currents in cultured endothelial cells. 779 12

Calcium and calcium dependent enzymes viz., calcium ATPase, protein kinase C and calcium activated neutral protease (milli CANP mCANP) were studied in the erythrocytes, platelets and lymphocytes of obligate carriers, in order to assess the usefulness of these indices for detection of carriers for Duchenne muscular dystrophy (DMD). With the exception of mCANP and lymphocyte calcium ATPase, other calcium dependent enzyme activities showed considerable overlap between carriers and control. Since the increase in the level of platelet mCANP was found in all affected boys (no false negatives) and obligate carriers, and patients with other myopathic conditions and some neurogenic causes did not show high platelet mCANP activity, this parameter could be considered as a good phenotypic index. Unlike SCK, the platelet mCANP of carriers did not overlap that of controls, hence tests are to be carried out to verify its usefulness as an index of carrier state in mutations other than DNA deletion since testing of non-deletion is both costly and has practical limitations.
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PMID:Importance of monitoring calcium & calcium related properties in carrier detection for Duchenne muscular dystrophy. 808 91

Many membrane traffic events that were previously thought to be constitutive recently have been found to be regulated by a variety of intracellular signaling pathways. The polymeric immunoglobulin receptor (pIgR) transcytoses dimeric IgA (dIgA) from the basolateral to the apical surface of polarized epithelial cells. Transcytosis is stimulated by binding of dIgA to the pIgR, indicating that the pIgR can transduce a signal to the cytoplasmic machinery responsible for membrane traffic. We report that dIgA binding to the pIgR causes activation of protein kinase C (PKC) and release of inositol 1,4,5-trisphosphate (IP3). The IP3 causes an elevation of intracellular Ca. Artificially activating PKC with phorbol myristate acetate or poisoning the calcium pump with thapsigargin stimulates transcytosis of pIgR, while the intracellular Ca chelator BAPTA-AM inhibits transcytosis. Our data suggest that ligand-induced signaling by the pIgR may regulate membrane traffic via well-known second messenger pathways involving PKC, IP3, and Ca. This may be a model of a general means by which membrane traffic is regulated by receptor-ligand interaction and signaling pathways.
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PMID:Signal transduction by the polymeric immunoglobulin receptor suggests a role in regulation of receptor transcytosis. 865 90

The effect of sphingosine on intracellular calcium signalling in glioma C6 cells was studied with Fura-2 video imaging technique. Sphingosine had a direct effect on changes in cytosolic Ca2+ concentration only when applied at high concentration of 100 microM, causing the cytosolic Ca2+ level to rise. However, at a much lower concentration of 15 microM sphingosine diminished calcium responses triggered by thapsigargin (a specific inhibitor of calcium pump in the endoplasmic reticulum) and ionomycin (calcium ionophore). Since responses to thapsigargin and ionomycin were blocked in Ca(2+)-free medium, we postulate that sphingosine is acting on the intracellular calcium stores. Additionally, sphingosine (at 15 microM and 100 microM) markedly decreases thapsigargin-induced sustained elevation in cytosolic Ca2+ concentration, indicating its inhibitory effect on thapsigargin-evoked Ca2+ influx. Sphingosine is a known inhibitor of protein kinase C and the involvement of this enzyme is postulated in the modulatory effects of sphingosine on intracellular calcium dynamics.
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PMID:Sphingosine stimulates calcium mobilization and modulates calcium signals evoked by thapsigargin in glioma C6 cells. 876

We have previously shown that two intracellular events which occur during capacitation of bovine sperm are the formation of actin filaments on the plasma and outer acrosomal membranes and the attachment of a PIP2-specific phospholipase C (PLC) to this membrane bound F-actin. This PLC plays an essential role in sperm exocytosis (acrosome reaction). In the present report, we further elucidated the role of this PLC using a PIP2-specific PLC of bacterial origin. This PLC is different from the endogenous sperm PLC in that it is calcium independent and not inhibited by neomycin. Here we report using bovine sperm that this bacterial PLC can restore actin release from extracted membranes as well as membrane fusion in a cell-free assay when the endogenous PLC is inhibited by neomycin. The sperm PLC requires 2 microM calcium for half maximal activation, while half maximal actin release from extracted plasma membranes occurs at 80 microM. Extracted sperm membranes were examined for calcium pumps and channels. Sperm plasma membranes were found to possess a thapsigargin insensitive calcium pump and calcium channels which are opened by phosphorylation by protein kinase C. The acrosomal membrane possesses a calcium pump which is inhibited by thapsigargin and calcium channels which are opened by cAMP. These observations are discussed in terms of a model of acrosomal exocytosis which involves a calcium rise that occurs in two stages resulting from calcium mobilization from internal stores followed by influx of extracellular calcium.
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PMID:Calcium mobilization and influx during sperm exocytosis. 883 17

We previously demonstrated that the antiprogestogen RU 486, when superfused on myometrial strips, induces a rapid decrease in spontaneous uterine contractile frequency, an increase in amplitude and duration of contractions, and a concomitant decrease in 6-keto PGF(1alpha) release. In this study, we present further work on the role of calcium transients and the involvement of the PLC/PKC pathway in mediating RU 486 effects. We found no clear causal relationship between the spontaneous contractility controlled by external Ca++ concentration and 6-keto PGF(1alpha) release depending mostly on intracellular Ca++ mobilization. We show that RU 486 strengthened the inhibitory effect of TMB8, a potent inhibitor of internal calcium, on both spontaneous contractility and 6-keto PGF(1alpha), release and antagonized the stimulatory action of thapsigargin, a toxin blocking the endoplasmic reticulum calcium pump (ER Ca++ ATPase). These data indicate that RU 486 could act as an inhibitor of intracellular Ca++ mobilization. A slight but significant decrease of the prostanoid liberation was observed in the presence of U73122, an inhibitor of PLC, but not in the presence of neomycin, another PLC inhibitory compound. PKC inhibitors, staurosporine and H7 did not significantly affect spontaneous 6-keto PGF1alpha release, showing that PIP2 hydrolysis and PKC pathway were not involved in the basal release of the prostacyclin metabolite. Vasopressin (AVP), an agent known to induce contractility of the non-pregnant human uterus, markedly increased 6-keto PGF(1alpha) release in a dose-dependent manner. Stimulation of GTP-regulated proteins (G proteins) by ALF4 was accompanied by a rise in 6-keto PGF(1alpha) liberation and a high contractile activity. The effects of both vasopressin and ALF4- were not significantly opposed by RU 486, indicating that other sources of Ca++, not controlled by the steroid, were involved in the agonist-stimulated prostanoid release. Studies with structurally related RU 486 analogues showed that the steroid effects were not dependent on their antihormonal activity, but rather on a specific 11beta arylsubstitution and a 17beta-hydroxy-13beta-methyl configuration of the 4,9-estradien-3-one molecule.
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PMID:RU 38486 inhibits intracellular calcium mobilization and PGI2 release from human myometrium: mechanisms of action. 900 39


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