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)

Cell activation of different cell types is accompanied by receptor-mediated stimulation of phospholipase C and a consequent breakdown of phosphatidylinositol 4,5-bisphosphate. Evidence suggests that GTP-binding proteins are involved in this signal transduction mechanism, which couples receptors to phospholipase C. Both the hydrolysis products diacylglycerol (DG) and inositol 1,4,5-trisphosphate (IP3) are intracellular messengers for cellular responses such as secretion, as illustrated by the pancreatic acinar cell. IP3 releases Ca2+ from a nonmitochondrial Ca2+ pool likely to be the endoplasmic reticulum (ER). This Ca2+ release leads to a transient rise in the cytosolic free Ca2+ concentration from approximately 100 to approximately 800 nmol/liter, by which enzyme secretion is initiated. For sustained secretion, Ca2+ influx into the cell is necessary to keep the cytosolic free Ca2+ concentration at a slightly elevated level. Activation of protein kinase C by DG and Ca2+ seems to play a major role in the second, sustained phase of secretion. Ca2+ reuptake into the ER and Ca2+ extrusion from the cell are achieved by (Ca2+ + Mg2+)-ATPase in both the ER and the plasma membrane as well as by an Na+/Ca2+ exchange in the latter. In the final step of exocytosis, protein phosphorylation by Ca2+-, DG-, and cAMP-dependent protein kinases is probably involved.
Soc Gen Physiol Ser 1987
PMID:The role of phosphatidylinositides in stimulus-secretion coupling in the exocrine pancreas. 314 61

The effect of elevating cytoplasmic Ca2+ [( Ca2+]i) on the intracellular pH (pHi) of thymic lymphocytes was investigated. In Na+-containing media, treatment of the cells with ionomycin, a divalent cation ionophore, induced a moderate cytoplasmic alkalinization. In the presence of amiloride or in Na+-free media, an acidification was observed. This acidification is at least partly due to H+ (equivalent) uptake in response to membrane hyperpolarization since: it was enhanced by pretreatment with conductive protonophores, it could be mimicked by valinomycin, and it was decreased by depolarization with K+ or gramicidin. In addition, activation of metabolic H+ production also contributes to the acidification. The alkalinization is due to Na+/H+ exchange inasmuch as it is Na+ dependent, amiloride sensitive, and accompanied by H+ efflux and net Na+ gain. A shift in the pHi dependence underlies the activation of the antiport. The effect of [Ca2+]i on Na+/H+ exchange was not associated with redistribution of protein kinase C and was also observed in cells previously depleted of this enzyme. Treatment with ionomycin induced significant cell shrinking. Prevention of shrinking largely eliminated the activation of the antiport. Moreover, a comparable shrinking produced by hypertonic media also activated the antiport. It is concluded that stimulation of Na+/H+ exchange by elevation of [Ca2+]i is due, at least in part, to cell shrinking and does not require stimulation of protein kinase C.
J Gen Physiol 1987 Feb
PMID:Cytoplasmic [Ca2+] and intracellular pH in lymphocytes. Role of membrane potential and volume-activated Na+/H+ exchange. 355 12

Although the human immunodeficiency virus type 1 (HIV-1) nef gene still has no precisely defined function, in vivo studies have demonstrated that Nef is an important pathogenic determinant of HIV. In order to identify cellular proteins capable of binding to Nef, the HIV-1LAI nef gene product was expressed in the bacterial vector pGEX-2T as a glutathione S-transferase (GST)-Nef fusion protein. Deletion mutants corresponding to 86 and 35 N-terminal residues of the Nef protein were prepared. The GST-Nef constructs were used to identify cellular kinases capable of interacting with Nef. After incubation with a Jurkat cell lysate, the GST-Nef constructs immobilized on glutathione-agarose beads bound to cellular kinase(s) and were phosphorylated at three sites in vitro: one on threonine at position 15, one on serine between residues 1 and 35, and one on threonine between residues 36 and 86. The Nef-phosphorylating activity was inhibited by protein kinase C (PKC)-selective inhibitors. Cell fractionation showed that this Nef-binding kinase was mainly in the membrane-associated fraction. These results suggest that kinase(s) of the PKC family are specifically bound to and phosphorylate Nef in vitro. The interaction of Nef with cellular kinases and its phosphorylation may be important in mediating the effects of Nef in HIV-1 pathogenesis.
J Gen Virol 1995 Jun
PMID:In vitro binding and phosphorylation of human immunodeficiency virus type 1 Nef protein by serine/threonine protein kinase. 754 Jan 94

1. Conflicting observations on the involvement of PKC in apoptosis point to a great variability depending on cell type, agent or condition causing apoptosis, phase of cell cycle and intracellular signaling pathway. 2. Inhibition by PKC of store-operated calcium entry mechanisms, which are sensitive to the oncoprotein bcl-2, should block the activation of calcium-dependent enzymes triggering the apoptotic cell death. 3. Activation of phosphatases by ceramide and inhibition of PKC by sphingosine seem to mediate the sphingomyelin pathway to apoptosis. 4. A putative target protein appears to be p34cdc2 which is regulated by a network of kinases and phosphatases. The uncoupling of timing for p34cdc2 activation and the completion of DNA replication results in the so-called "mitotic catastrophe" that shares some features with apoptosis.
Gen Pharmacol 1995 Sep
PMID:Protein kinase C involvement in apoptosis. 755 62

1. Aluminum is neurotoxic in humans and animals and alters formation of inositol phosphate (IP) second messengers following in vivo or in vitro exposure. 2. Several components of the IP signalling system including G-proteins, phosphatidylinositol-specific phospholipase C (PI-PLC), protein kinase C (PKC) and Ca2+ homeostasis are susceptible to inhibition/disruption by aluminum compounds. 3. Recent evidence suggests that, despite its effects on other components, competitive inhibition by aluminum of phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis by PI-PLC underlies its effects on agonist-stimulated IP generation.
Gen Pharmacol 1995 Sep
PMID:Effects of aluminum on neuronal signal transduction: mechanisms underlying disruption of phosphoinositide hydrolysis. 755 63

1. The actions of diadenosine polyphosphates, diadenosine tetraphosphate (Ap4A), diadenosine pentaphosphate (Ap5A) and diadenosine hexaphosphate (Ap6A) in the nervous system have been reviewed. 2. In the peripheral nervous system, diadenosine polyphosphates bind to P2-purinergic receptors such as the P2Y in chromaffin cells and Torpedo synaptosomes, P2X in vas deferens and urinary bladder and also Torpedo synaptosomes and P2U in endothelial chromaffin cells. 3. In the central nervous system ApnA compounds can act through P2X-purinoceptors opening cation channels in nodose ganglion neurones. Diadenosine polyphosphates bind to a P2d-purinergic receptor in rat brain synaptic terminals and hippocampus, linked to protein kinase C (PKC) activation. 4. P4-purinoceptors are specific receptors for diadenosine polyphosphates, coupled to the Ca2+ influx, in the central synapses. This purinoceptor is not activated by ATP and synthetic analogs. The P4-purinoceptor could act as a positive modulator of the synaptic transmission, giving even more importance to diadenosine polyphosphates as neurotransmitters.
Gen Pharmacol 1995 Mar
PMID:P2 purinergic receptors for diadenosine polyphosphates in the nervous system. 759 71

1. Effects of isoprenaline (ISO), carbachol and phorbol ester (a stimulator of protein kinase C) on L-type Ca2+ channels in single cultured rat aortic vascular smooth muscle (A7r5) cells were examined using whole-cell voltage clamp (at room temperature 22 degrees C). 2. With 20 mmol/l Ca2+ in the bath solution and 10 mmol/l EGTA in the pipette solution, a slow ICa (L-type) current was observed in the A7r5 cell line, which was blocked by nifedipine (2 mumol/l). 3. ISO (5 mumol/l) inhibited ICa by 18.3 +/- 2.2% (P < 0.001), and carbachol (1 mumol/l) also decreased ICa by 15.0 +/- 3.2% (P < 0.01). 8-Br-cAMP (1 mmol/l) and 8-Br-cGMP (1 mmol/l) both inhibited ICa by 30.1 +/- 2.8% (P < 0.001) and 18.8 +/- 3.8% (P < 0.01), respectively. 4. Phorbol ester, 4-beta-phorbol-12, 13-dibutyrate (PDB), at 0.1-1 mumol/l, had almost no effect on ICa in most cells, but slightly potentiated (or slightly enhanced) the inhibitory effects of ISO. 5. Time decay (inactivation) of ICa consisted of two exponentials. Both the fast and slow time constants were slightly prolonged by ISO (5 mumol/l), and by carbachol (1 mumol/l); PDB (1 mumol/l) slightly shortened the fast time constant only. The half-maximum voltages of inactivation were not significantly affected by any of the agents. 6. These results suggest that the L-type ICa current is modulated by cyclic nucleotides (cAMP and cGMP) and by PK-C stimulation, and thereby contribute to regulation of contraction of the vascular smooth muscle cells.
Gen Pharmacol 1995 Mar
PMID:Modulation of L-type Ca2+ current by isoprenaline, carbachol and phorbol ester in cultured rat aortic vascular smooth muscle (A7r5) cells. 759 90

1. Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is a non-toxic seleno-organic drug with antiinflammatory, antiatherosclerotic and cytoprotective properties. 2. Ebselen and some of its metabolites are effective reductants of hydroperoxides including those arising in biomembranes and lipoproteins. 3. By reactions with hydroperoxides and thiols several interconversion cycles are formed which include ebselen metabolites with varying oxidation number of the selenium. 4. In the presence of thiols ebselen mimics the catalytic activities of phospholipid hydroperoxide glutathione peroxidase. 5. Ebselen inhibits at low concentrations a number of enzymes involved in inflammation such as lipoxygenases, NO synthases, NADPH, oxidase, protein kinase C and H+/K(+)-ATPase. The inhibitions are manifested on the cellular level and may contribute to the antiinflammatory potential of ebselen.
Gen Pharmacol 1995 Oct
PMID:Molecular actions of ebselen--an antiinflammatory antioxidant. 759 Jan 3

1. beta-Alanyl-L-histidinato zinc (AHZ), in which zinc is chelated to beta-alanyl-L-histidine, is a new zinc compound. beta-Alanyl-L-histidine can uniquely chelated zinc ion in various essential trace metals. More recently, it has been demonstrated that this compound has more intensive effect than zinc sulfate on bone metabolism, suggesting a role as pharmacological tool in osteoporosis. This review describes mainly the action of AHZ on bone resorption as summarized in the following. 2. The prolonged oral administration of AHZ (10-100 mg/kg/day) can completely prevent bone loss in the femur of ovariectomized rats, indicating the preventive effect of AHZ on bone resorption in vivo. 3. The decrease in bone calcium content induced by various bone resorbing factors was completely inhibited by the presence of AHZ (10(-6)-10(-4) M) in bone tissue culture system in vitro. 4. Many bone resorbing agents can stimulate the formation (differentiation) of osteoclasts from marrow cells. AHZ (10(-6)-10(-4) M) clearly inhibited osteoclast-like cell formation in mouse marrow culture in vitro. 5. AHZ may act on the process of parathyroid hormone-induced protein kinase C activation which is involved in Ca(2+)-signaling in osteoclastic cells.
Gen Pharmacol 1995 Oct
PMID:beta-Alanyl-L-histidinato zinc and bone resorption. 759 Jan 5

1. Recent data suggesting that the human neuroblastoma SH-SY5Y is a suitable cell line in which to study the effect of second messengers on NA release are discussed in the context of current views on exocytosis. 2. Release of NA is evoked by depolarization, as well as activation of muscarinic (M3) and bradykinin (B2) receptors in SH-SY5Y cells which have not been differentiated by the addition of growth factors. 3. Evoked release is enhanced by activation of protein kinase C. 4. Activation of protein kinase C decreases the changes in intracellular calcium evoked by carbachol, bradykinin and 100 mM K+. 5. SH-SY5Y express N-type and L-type voltage sensitive Ca2+ channels. L-Type Ca(2+)-channels are coupled to NA release under conditions of weak depolarization. However with strong depolarization (100 mM K+) both L-type and N-type channels are involved. 6. Muscarinic- and neuropeptide Y receptors are coupled to the inhibition of Ca2+ channel activity.
Gen Pharmacol 1995 Oct
PMID:The use of the human neuroblastoma SH-SY5Y to study the effect of second messengers on noradrenaline release. 759 Jan 7


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