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)

The relative roles of protein kinase C in regulating excitatory amino acid-, cholinoceptor-, and adrenoceptor-stimulated phosphoinositide hydrolysis were studied. Slices of rat hippocampus were prelabeled with [3H]-myo-inositol, and agonist-induced [3H]-phosphoinositide hydrolysis was measured by the formation of [3H]-inositol monophosphate ([3H]-IP) in the presence of lithium ion. Activation of protein kinase C with phorbol 12,13-dibutyrate (PDB) (10(-6) M) completely inhibited ibotenate (IBO) (10(-3) M)-induced [3H]-phosphoinositide hydrolysis. Half-maximal inhibition was observed at about 10(-7) M PDB. Higher concentrations of PDB were required to inhibit stimulation of [3H]-IP by either carbachol (CARB) (10(-3) M) or norepinephrine (NE) (10(-4) M, and only partial inhibition could be attained. Preincubation with staurosporine (STAURO) (10(-5) M) or 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) (10(-4) M), inhibitors of protein kinase C, potentiated IBO- but not CARB- or NE-induced stimulation of [3H]-IP. PDB inhibition of IBO- or NE-stimulated [3H]-phosphoinositide hydrolysis was reversed by co-addition of STAURO or H-7. In the case of IBO + STAURO, this reversal was to the potentiated level observed with STAURO alone. Enhanced agonist stimulation and reversal of PDB inhibition were also produced by STAURO when [3H]-phosphoinositide hydrolysis was stimulated by either L-glutamate or quisqualate. These experiments show that direct activation of protein kinase C by PDB leads to inhibition of phosphoinositide hydrolysis mediated by excitatory amino acid receptors, cholinoceptors, or adrenoceptors. However, the enhanced agonist-stimulated phosphoinositide hydrolysis elicited by inhibitors of protein kinase C suggests that, when protein kinase C is indirectly activated, only excitatory amino acids rapidly inhibit further receptor-coupling.
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PMID:Selective inhibition of excitatory amino acid-stimulated phosphoinositide hydrolysis in the rat hippocampus by activation of protein kinase C. 290 66

In immature rat cerebellar slices in vitro, a long term depression (LTD) of the responses of Purkinje cells (PCs) to L-glutamate (Glu) was achieved in 30% of the recorded cells by simultaneous stimulation of the neurones by Glu and by climbing fibres (CFs). This effect was not observed for L-aspartate (Asp)-induced responses. Similarly, selective LTD of Glu-induced responses was obtained in 22% of the cells by pairing Glu applications with direct stimulation of the cells which elicited calcium spikes in these neurones. Finally, bath application of phorbol esters also induced a selective LTD of Glu-induced responses in all cells tested. These results suggest that protein kinase C is involved in cerebellar synaptic plasticity.
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PMID:Activation of protein kinase C induces a long-term depression of glutamate sensitivity of cerebellar Purkinje cells. An in vitro study. 290 1

The actions and interactions of the neurotransmitter glutamate and the intracellular messengers calcium, cyclic AMP, and protein kinase C (PKC) in the regulation of neurite outgrowth and cell survival were examined in hippocampal pyramidal-like neurons in isolated cell culture. Low, subtoxic levels of glutamate (10-100 microM) caused the regression of dendrites but not axons; millimolar levels caused cell death. Calcium ionophore A23187 (50-100 nM) and the PKC activator phorbol-12-myristate-13-acetate (PMA; 10-50 nM) caused the regression of both axons and dendrites, whereas the adenylate cyclase activator forskolin enhanced outgrowth rates in both axons and dendrites. The effects of glutamate, A23187, PMA, and forskolin on outgrowth were mediated locally at the growth cones; dendrites were more sensitive than axons to each of these agents. High levels of A23187 (1 microM) or PMA (100 nM) significantly reduced cell survival. Co2+ and trifluoperazine each significantly reduced glutamate-induced dendritic regression and neurotoxicity suggesting that calcium influx and/or PKC activation mediated glutamate's actions. Fura-2 measurements showed that glutamate caused a rapid rise in intracellular calcium levels; this rise was prevented by Co2+. PMA and forskolin did not alter intracellular calcium levels, nor did these agents affect glutamate-induced calcium rises. Taken together, the results indicate that parallel intracellular messenger pathways that influence neurite outgrowth and cell survival are operative in hippocampal neurons; these messengers may play roles in the formation and modification of neuronal circuitry.
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PMID:Intracellular messengers in the generation and degeneration of hippocampal neuroarchitecture. 290 49

A synthetic random polymer of threonine and glutamate (1:4.4) is readily phosphorylated by protein kinase P but not by five other protein-serine (threonine) kinases. A synthetic random polymer of serine and arginine (1:3) is readily phosphorylated by protein kinase A and protein kinase C but not by protein kinase P. Although the amino acid sequences surrounding the phosphorylated serine (threonine) residue have been demonstrated in studies with small synthetic polypeptides to be decisive factors in the rate at which they are phosphorylated, the findings with the large synthetic polypeptides suggest that in the case of proteins the size, the tertiary structure, and particularly the electrostatic interactions are equally or more important contributing factors. Syringomycin, a toxin from Pseudomonas syringae, and polymyxin B, from Bacillus polymyxa, stimulate protein kinase P, strongly inhibit protein kinase C, and have no effect on protein kinase A. Basic polypeptides with high lysine content are phosphorylated by ATP nonenzymatically.
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PMID:Phosphorylation of synthetic random polypeptides by protein kinase P and other protein-serine (threonine) kinases and stimulation or inhibition of kinase activities by microbial toxins. 312 47

A phosphoprotein expressed in rat brain is closely related to the 80 kDa substrate of protein kinase C present in 3T3 cells. The protein kinase C substrates from both sources migrate identically on two-dimensional gel electrophoresis and give similar phosphopeptide fragments when digested with protease. Using a series of chromatographic steps, including DEAE-cellulose chromatography, Sephadex G150 gel filtration and reverse phase fast protein liquid chromatography, this phosphoprotein was purified 3800-fold from rat brain. The preparation appears homogenous by one- and two-dimensional gel electrophoresis, is an effective substrate of protein kinase C and contains a high proportion of the acidic amino acids glutamate and aspartate, and of alanine.
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PMID:Purification of a phosphoprotein from rat brain closely related to the 80 kDa substrate of protein kinase C identified in Swiss 3T3 fibroblasts. 336 Jan 39

Tumor-promoting phorbol esters specifically activate protein kinase C and mimic the effects of neurotransmitters in certain systems. Treatment of hippocampal slices with phorbol dibutyrate caused translocation of protein kinase C activity from cytoplasm to membranes. Experiments with carbachol, norepinephrine, glutamate, KCl, and LiCl failed to demonstrate a similar translocation. Translocation more readily provides an index of protein kinase C involvement for phorbol esters than for other agents in hippocampus.
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PMID:Translocation of protein kinase C in rat hippocampal slices. 346 26

The 87-kDa protein, a major specific substrate for protein kinase C, has been purified 500-fold to apparent homogeneity from bovine forebrain supernatant. The purification procedure included batch adsorption to DE-52 (DEAE-cellulose), (NH4)2SO4 precipitation, and chromatography on DEAE-Sephacel, Bio-Gel HTP (hydroxylapatite), Sephacryl S-400, and fast protein liquid chromatography ProRPC. The amino acid composition was notable for its high proportion of alanine (28.6 mol%) and its enrichment in glutamate/glutamine (18.1 mol%), glycine (12.6 mol%), and proline (11.3 mol%). The partial specific volume was 0.702 ml/g; the Stokes radius and sedimentation coefficient were 85 A and 2.11 S, respectively. Although the relative molecular mass of the protein on NaDodSO4/8% PAGE was 87-90 kDa, the molecular mass as determined from the above values was 68 kDa. The frictional ratio was 3.2, and the axial ratio was 60, indicating that the 87-kDa protein is an extremely elongated monomer. The purified 87-kDa protein was phosphorylated by purified protein kinase C to a stoichiometry of 2.2 mol of 32P per mol of 87-kDa protein (calculated using a value of 68 kDa for the molecular mass). Phosphorylation was exclusively on serine residues.
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PMID:The 87-kDa protein, a major specific substrate for protein kinase C: purification from bovine brain and characterization. 347 78

We have reported previously that a selective metabotropic glutamate receptor agonist, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), caused two primary postsynaptic membrane changes, namely, a slow membrane depolarization, and burst firing in rat dorsolateral septal nucleus neurons. In addition, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid also potentiates a slow after depolarization in rat dorsolateral septal nucleus neurons. We now report that, among all the postsynaptic membrane changes induced by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, only the burst firing was selectively blocked by pertussis toxin pretreatment. Thus, aminocyclopentane-1,3-dicarboxylic acid induced burst firing was mediated by a metabotropic receptor coupled to a pertussis toxin-sensitive GTP-binding protein, while the other induced cellular responses may be mediated by metabotropic glutamate receptors insensitive to pertussis toxin. We further characterized this receptor pharmacologically. This metabotropic receptor is activated by several metabotropic glutamate receptor agonists, but is insensitive to L-glutamate or L-aspartate. On the basis of its agonist activity profile, particularly the ineffectiveness of glutamate as an agonist, we have tentatively assigned the name aminocyclopentane-1,3-dicarboxylic acid metabotropic receptor, to this native, pertussis toxin-sensitive metabotropic receptor in the dorsolateral septal nucleus. Furthermore, this receptor is coupled to protein kinase C, probably via a phospholipase C independent pathway.
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PMID:(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-induced burst firing is mediated by a native pertussis toxin-sensitive metabotropic receptor at rat dorsolateral septal nucleus neurons. 747 53

Both experimental traumatic brain injury and clinical traumatic brain injury appear to render the brain more vulnerable to a second ischemic insult. The mechanisms of enhanced vulnerability to subsequent ischemia appear to include a reduced ability to increase cerebral blood flow in response to hypotension, hypoxemia, or acute anemia and increased tissue sensitivity to ischemia. Although numerous mediators may be involved in increased tissue sensitivity, those that particularly merit investigation include oxygen free radicals, glutamate, arachidonate metabolites, calcium ions, and protein kinase C.
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PMID:Enhanced vulnerability to secondary ischemic insults after experimental traumatic brain injury. 749 45

We have investigated the action of norepinephrine (NE) on excitatory synaptic transmission in the hippocampus by recording from CA3 pyramidal cells in organotypic slice cultures. NE (5 microM) was found to decrease the amplitude of pharmacologically isolated EPSPs elicited with stimulation of mossy fibers or recurrent axon collaterals (mean decrease in EPSP amplitude, 44%). Desensitization was observed with repetitive applications. NE did not affect the sensitivity of CA3 cells to iontophoretically applied AMPA, and did not affect the amplitude distribution of TTX-resistant, miniature excitatory synaptic currents. These data suggest that NE acts at presynaptic receptors to decrease glutamate release. This action of NE was blocked by the alpha receptor antagonist phentolamine and the specific alpha 1 receptor antagonist prazosine, but not by the beta receptor antagonist timolol or the alpha 2 receptor antagonist idazoxan. Inhibition of EPSPs by NE was prevented by pretreatment of cultures with pertussis toxin, indicating that G-proteins couple these receptors to their effectors. Stimulation of protein kinase C with phorbol ester blocked the action of NE on EPSPs. This effect, as well as the desensitization of NE responses, was reduced by application of the protein kinase inhibitor staurosporin. Presynaptic inhibition of excitatory synaptic transmission, mediated by alpha adrenergic receptors, represents a novel modulatory action of NE in the hippocampus.
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PMID:Presynaptic inhibition of excitatory synaptic transmission mediated by alpha adrenergic receptors in area CA3 of the rat hippocampus in vitro. 750 23


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