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)

Activation of protein kinase C (PKC) in Aplysia bag cell neurons causes the recruitment of voltage-dependent calcium channels. Using imaging techniques on isolated cells, we have now found that an activator of PKC, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), promotes the rapid appearance of new sites of calcium influx associated with a change in the morphology of neurite endings. In untreated cells, calcium influx triggered by action potentials occurs along neurites and in the central region of growth cones, but does not usually occur at the leading edge of lamellipodia. TPA produces extension of the lamellipodium, and action potentials now trigger calcium influx at the distal edge of the newly extended endings. Cotreatment with TPA and a cyclic AMP analog promotes movement of secretory organelles toward the new sites of calcium influx. Our results suggest that these second messenger systems promote the rapid formation of morphological structures that contribute to the potentiation of peptide release.
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PMID:Recruitment of Ca2+ channels by protein kinase C during rapid formation of putative neuropeptide release sites in isolated Aplysia neurons. 131 64

The modulation of evoked transmitter release by presynaptic receptors was studied at an identified cholinergic synapse in the buccal ganglion of Aplysia. Two auto-receptors affecting acetylcholine release in opposite ways were identified. Additionally acetylcholine (ACh) release was found to be facilitated by the peptide FLRFamide and inhibited by histamine. Ca2+ channels appeared as the final effectors controlled by these non-cholinergic presynaptic receptors whereas the activation of cholinergic presynaptic receptors did not affect the Ca2+ influx. The intracellular pathway activated by FLRFamide receptors was investigated in detail. The facilitation of transmitter release induced by this peptide was prevented by bath application of H-7, a protein kinase C inhibitor. Moreover, a diacylglycerol analog mimicked the action of FLRFamide. These results suggest that activation of protein kinase C leading to the phosphorylation of Ca2+ channels could be the mechanism through which presynaptic FLRFamide receptors increase evoked quantal release of acetylcholine at this synapse.
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PMID:Regulation of transmitter release by presynaptic receptors at a cholinergic neuro-neuronal synapse. 133 57

Two second messenger pathways, one that uses the cAMP-dependent protein kinase A (PKA), the other that uses protein kinase C (PKC), have been found to contribute to the short-term presynaptic facilitation of the connections between the sensory neurons in Aplysia and their target cells, the interneurons and motor neurons of the gill-withdrawal reflex. To study their relative contributions as a function of the previous history of the neuron's activity, we have examined the effects of inhibiting PKA (using Rp-cAMPS) and PKC (using H7) on the short-term facilitation of spontaneous release as well as of the evoked release induced by serotonin at nondepressed, partially depressed, and highly depressed synapses. Our results suggest that whereas activation of PKA is sufficient to trigger the facilitation of nondepressed synapses, activation of both PKA and PKC is required to facilitate depressed synapses, with the contribution of PKC becoming progressively more important as synaptic transmission becomes more depressed.
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PMID:Roles of PKA and PKC in facilitation of evoked and spontaneous transmitter release at depressed and nondepressed synapses in Aplysia sensory neurons. 135 77

The effects of the dihydropyridine (DHP) Ca2+ channel antagonist, nifedipine, were studied on the cholinergic synapse between the presynaptic neurones B4/B5 and the postsynaptic neurones B3/B6 located in the buccal ganglion of Aplysia californica. Nifedipine (10 microM) decreased the presynaptic Ca2+ current by 30%-40%. Blockade of DHP-sensitive Ca2+ channels, however, did not affect quantal transmitter release from the presynaptic neurones. Thus, at this synapse, DHP-sensitive Ca2+ channels appear not to be involved in acetylcholine (ACh) release. The postsynaptic response to an ionophoretic application of ACh was decreased by nifedipine, pointing to a blocking action of the drug on the postsynaptic receptor/channel complex. Nifedipine was also found to activate protein kinase C, which in turn induces an increase in the nifedipine-resistant presynaptic Ca2+ influx and in the number of released ACh quanta. These effects of nifedipine could be prevented by a previous application of 1,5-(isoquinolinylsulfonyl)-2-methyl-piperazine (H-7), a protein kinase blocker.
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PMID:Pre- and postsynaptic actions of nifedipine at an identified cholinergic central synapse of Aplysia. 136 8

1. The electrophysiological properties of the sensory neurons that mediate withdrawal reflexes in Aplysia are modulated by a number of second messengers. For example, the second messengers adenosine 3',5'-cyclic monophosphate (cAMP) and arachidonic acid modulate the S-K+ current (IK,S) and the calcium-activated K+ current (IK,Ca). Recent evidence suggests that protein kinase C (PKC) may also be an important regulator of cellular plasticity. In the present study we examined the possibility that IK,Ca was modulated by the activation of PKC in the pleural sensory neurons. 2. In voltage-clamped sensory neurons the application of phorbol esters, such as phorbol dibutyrate (PDBu), phorbol myristate (PMA), and phorbol diacetate (PDAc), which activate PKC, caused a dose-dependent increase in a voltage-dependent current with properties that resembled IK,Ca. The inactive isomer of phorbol ester, 4 alpha-phorbol, was without effect. 3. This phorbol ester-sensitive current had the kinetics and pharmacological sensitivity of IK,Ca. The current developed slowly during step depolarizations, showed little inactivation, and was activated at membrane potentials greater than approximately 0 mV. In addition, the current modulated by phorbol esters was blocked by a concentration of tetraethylammonium (TEA) that blocks a component of IK,Ca in the sensory neurons. 4. IK,Ca, which was activated directly by the iontophoretic injection of Ca2+, was also enhanced by PDBu. Moreover, the enhancement of Ca(2+)-elicited responses by PDBu persisted after Ca2+ influx was blocked by cobalt. These results indicate that at least one component of the modulation of IK,Ca by PDBu was independent of the modulation of voltage-dependent Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of IK,Ca by phorbol ester-mediated activation of PKC in pleural sensory neurons of Aplysia. 143 69

1. Plasticity at the connections between sensory neurons and their follower cells in Aplysia has been used extensively as a model system to examine mechanisms of simple forms of learning. Earlier studies have concluded that serotonin (5-HT) is a key modulatory transmitter and that it exerts its short-term actions via cAMP-dependent activation of protein kinase A. Subsequently, it has become clear that other kinase systems such as protein kinase C (PKC) also may be involved in the actions of 5-HT. 2. Application of phorbol esters, which activate PKC, produced a slowly developing spike broadening but had little effect on excitability (a process known to be primarily cAMP dependent). Moreover, the effects of phorbol esters and 5-HT on spike duration were not additive, suggesting that they may share some common mechanisms. 3. The protein kinase inhibitor staurosporine suppressed both 5-HT-induced slowly developing spike broadening and, under certain conditions, facilitation of transmitter release. Staurosporine did not inhibit 5-HT-induced enhancement of excitability. The effectiveness of staurosporine on spike broadening was dependent on the time at which spike broadening was examined after application of 5-HT. Staurosporine appeared to have little effect on spike broadening 3 min after application of 5-HT, whereas it inhibited significantly 5-HT-induced spike broadening at later times. The staurosporine-insensitive component of 5-HT-induced spike broadening may be mediated by cAMP. 4. The results suggest that the activation of PKC plays a key role in components of both 5-HT-induced spike broadening and facilitation of synaptic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of protein kinase C in serotonin-induced spike broadening and synaptic facilitation in sensorimotor connections of Aplysia. 152 80

Ca(2+)-activated and Ca(2+)-independent protein kinase Cs (PKCs) are present in the nervous system of the marine mollusk Aplysia californica (Kruger et al., 1991). Sensitizing stimuli or application of the facilitatory transmitter 5-HT to intact isolated ganglia produces the presynaptic facilitation of sensory-to-motor neuron synapses that underlies behavioral sensitization, which is a simple form of learning. Activation of PKC can also produce this presynaptic facilitation (Braha et al., 1990). To determine which type of PKC is activated, we developed a sensitive and selective assay to measure both Ca(2+)-activated and Ca(2+)-independent PKC activities in crude supernatant and membrane fractions of nervous tissue. This assay is based on the specific binding of the Ca(2+)-activated PKCs to phosphatidylserine vesicles in the presence of Ca2+ and makes use of a novel synthetic peptide with sequences conforming to phylogenetically conserved pseudosubstrate regions of the Ca(2+)-independent kinases. We provide evidence that the presynaptic facilitation is produced by a Ca(2+)-activated isoform: application of 5-HT increases the amount of the Ca(2+)-activated PKC activity associated with the membrane. Under these conditions, no increase in Ca(2+)-independent kinase activity is seen.
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PMID:Selective activation of Ca(2+)-activated PKCs in Aplysia neurons by 5-HT. 155 91

We describe some properties on an Mr 30,000 thermolabile and trypsin-sensitive protein that activates phospholipase A2 (PLA2) and which was isolated from nervous tissue of the marine mollusk, Aplysia californica. A similar protein is present in rat cerebral cortex. This protein was partially purified from crude homogenates of nervous tissue by ion exchange chromatography on DEAE-Sephadex followed by size-exclusion high performance liquid chromatography (HPLC). It is loosely associated with membrane fractions, and is extracted by 0.05% Tween 20. Although similar in size to several previously described PLA2-stimulating proteins from non-neural mammalian cells and tissues, it differs from them in some aspects of biological activity. The protein promotes the release of eicosanoids from the membranes of intact Aplysia neurons prelabeled with [3H]arachidonic acid and appears to be an in vitro substrate for protein kinase C (PKC). PLA2-stimulating activity is greatly enhanced after exposing isolated ganglia to phorbol dibutyrate (PDBu) and is reduced by treatment with immobilized E. coli alkaline phosphatase. These observations suggest that phosphorylation of this stimulatory protein by PKC regulates PLA2 in neurons.
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PMID:A phospholipase A2-stimulating protein regulated by protein kinase C in Aplysia neurons. 164 37

We isolated cDNA clones from an Aplysia sensory-cell library encoding two isoforms of protein kinase C (PKC). Several isozyme-specific regions are conserved in the Aplysia kinases, notably the variable regions V5 in the Ca(2+)-dependent PKC (Apl I) and V1 in the Ca(2+)-independent PKC (Apl II). Neuronal proteins with the properties expected of these two isoforms can be identified with antibodies raised against peptides synthesized from the amino acid sequences deduced from the clones. Sacktor and Schwartz (1990) measured the proportion of kinase activity that can be translocated to membrane in Aplysia sensory neurons and ganglia by stimuli that produce the presynaptic facilitation underlying behavioral sensitization. Much less Apl I and Apl II are translocated, suggesting that still other isoforms of PKC exist in these cells.
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PMID:Cloning and characterization of Ca(2+)-dependent and Ca(2+)-independent PKCs expressed in Aplysia sensory cells. 186 17

Facilitation of the monosynaptic connection between siphon sensory neurons and gill and siphon motor neuron contributes to sensitization and dishabituation of the gill and siphon withdrawal reflex in Aplysia. The facilitatory transmitter serotonin (5-HT) initiates two mechanisms that act in parallel to increase transmitter release from siphon sensory neurons. 5-HT acts, at least partly through cAMP, to broaden the presynaptic action potential. 5-HT also initiates a second process that facilitates depressed sensory neuron synapses by a mechanism independent of changes in action potential duration. Recent experiments indicated that either of two protein kinases, cAMP-dependent protein kinase A and protein kinase C, are capable of effectively activating this second facilitatory mechanism, restoring synaptic transmission in depressed synapses. We have used the adenylyl cyclase inhibitor SQ 22,536 [9-(tetrahydro-2-furyl)adenine or THFA] to explore the contribution of cAMP to the reversal of synaptic depression. THFA effectively inhibited both adenylyl cyclase activity in vitro and known cyclase-mediated effects in intact sensory neurons. THFA also completely blocked facilitation of depressed synapses by 5-HT. These results suggest that adenylyl cyclase plays a critical role in the reversal of synaptic depression that contributes to dishabituation in this system.
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PMID:Reversal of synaptic depression by serotonin at Aplysia sensory neuron synapses involves activation of adenylyl cyclase. 192 65


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