Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this report we describe changes in the intracellular redistribution of raf serine/threonine protein kinase (product of the raf proto-oncogene family) in hippocampal neurons following cerebral ischemia in Mongolian gerbils. For immunohistochemical localization studies polyclonal antisera specific for each of the A, B, and Raf-1 isotypes of raf, as well as a pan-raf antisera, were employed. Of these, only sera recognizing B-raf, as well as the general v-raf (raised against the conserved C-terminal region) were positive, indicating that B-raf is the major isotype in this neuronal region. Three different ischemic models were used (repeated 3 times for two min and single 5 or 15 min occlusions, of the common carotid arteries) to demonstrate that ischemic insult causes redistribution of raf protein kinase into the cell nucleus of hippocampal neurons. Increased amounts of raf protein in the nuclei of pyramidal cells following ischemia was confirmed by Western blot analysis of isolated nuclear fractionations. Moreover, an elevation in the level of nuclear raf protein also was detected in the contralateral (i.e. non-occluded hemisphere) neurons of CA1 and CA3 subfields 4 days after the ischemic insult indicating a possible transsynaptic increase in the amount of raf protein along with redistribution. The intranuclear translocation of the immunoreactive material started from the perinucleolar rim and with time extended throughout the nucleus. Enhanced levels and altered redistribution of the raf polypeptide in the nuclei of pyramidal cells of the CA3 subfield appears to be reversible and returns to the normal level 12 days following the ischemic insult.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Cerebral ischemia induces transient intracellular redistribution and intranuclear translocation of the raf proto-oncogene product in hippocampal pyramidal cells. 206 47

We have shown that the induction but not maintenance of long-term potentiation (LTP) in the Schaffer collateral-CA1 synaptic zone of the rat hippocampus is blocked by the extracellular application of the protein kinase inhibitor staurosporine. This compound was also found to block the induction of LTP in the perforant path-granule cell synaptic zone of the intact hippocampus. We have determined that staurosporine is membrane-permeable and can be detected inside cells by fluorescence microscopy. When cultured fetal hippocampal neurons were treated with staurosporine, fluorescence was observed throughout the cytoplasm and in neurites. Other cell types gave similar results. It has been proposed that constitutively active cytosolic protein kinase M or other protein kinases maintain long-term potentiation. Since staurosporine has access to the cytosol and inhibits protein kinase M in vitro, our results suggest that this enzyme is not responsible for the maintenance of LTP. This conclusion may extend to other protein kinases as well, since staurosporine has been shown to inhibit a variety of these enzymes.
...
PMID:Evidence that protein kinase M does not maintain long-term potentiation. 207 82

The protective effects of protein kinase inhibitors and a calmodulin kinase inhibitor (W-7) against ischemic neuronal damage were examined in the CA1 subfield of the hippocampus. Staurosporine, KT5720, and KT5822 were used as inhibitors of protein kinase C (PKC), cyclic AMP-dependent protein kinase, and cyclic GMP-dependent protein kinase, respectively. All test compounds were injected topically into the CA1 subfield of the hippocampus. In the gerbil ischemia model, staurosporine (0.1-10 ng) administered 30 min before ischemia prevented neuronal damage in a dose-dependent manner. However, KT5720, KT5822, and W-7 were ineffective, even at a dose of 10 ng. In the rat ischemia model, staurosporine (10 ng) also prevented neuronal damage when administered before ischemic insult, although staurosporine administered 10 or 180 min after recirculation was ineffective. These results suggest the involvement of PKC in CA1 pyramidal cell death after ischemia and that the fate of vulnerable CA1 pyramidal cells through PKC-mediated processes could be determined during the early recirculation period.
...
PMID:Staurosporine, a novel protein kinase C inhibitor, prevents postischemic neuronal damage in the gerbil and rat. 238 38

The phenomenon of long-term potentiation (LTP), a long lasting increase in the strength of synaptic transmission which is due to brief, repetitive activation of excitatory afferent fibres, is one of the most striking examples of synaptic plasticity in the mammalian brain. In the CA1 region of the hippocampus, the induction of LTP requires activation of NMDA (N-methyl-D-aspartate) receptors by synaptically released glutamate with concomitant postsynaptic membrane depolarization. This relieves the voltage-dependent magnesium block of the NMDA-receptor ion channel, allowing calcium to flow into the dendritic spine. Although calcium has been shown to be a necessary trigger for LTP (refs 11, 12), little is known about the immediate biochemical processes that are activated by calcium and are responsible for LTP. The most attractive candidates have been calcium/calmodulin-dependent protein kinase II (CaM-KII) (refs 13-16), protein kinase C (refs 17-19), and the calcium-dependent protease, calpain. Extracellular application of protein kinase inhibitors to the hippocampal slice preparation blocks the induction of LTP (refs 21-23) but it is unclear whether this is due to a pre- and/or postsynaptic action. We have found that intracellular injection into CA1 pyramidal cells of the protein kinase inhibitor H-7, or of the calmodulin antagonist calmidazolium, blocks LTP. Furthermore, LTP is blocked by the injection of synthetic peptides that are potent calmodulin antagonists and inhibit CaM-KII auto- and substrate phosphorylation. These findings demonstrate that in the postsynaptic cell both activation of calmodulin and kinase activity are required for the generation of LTP, and focus further attention on the potential role of CaM-KII in LTP.
...
PMID:An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation. 254 23

Long-term potentiation (LTP) of synaptic transmission is a widely studied cellular example of synaptic plasticity. However, the identity, localization, and interplay among the biochemical signals underlying LTP remain unclear. Intracellular microelectrodes have been used to record synaptic potentials and deliver protein kinase inhibitors to postsynaptic CA1 pyramidal cells. Induction of LTP is blocked by intracellular delivery of H-7, a general protein kinase inhibitor, or PKC(19-31), a selective protein kinase C (PKC) inhibitor, or CaMKII(273-302), a selective inhibitor of the multifunctional Ca2+-calmodulin-dependent protein kinase (CaMKII). After its establishment, LTP appears unresponsive to postsynaptic H-7, although it remains sensitive to externally applied H-7. Thus both postsynaptic PKC and CaMKII are required for the induction of LTP and a presynaptic protein kinase appears to be necessary for the expression of LTP.
...
PMID:Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP. 254 38

The adenylate cyclase system has been studied from the standpoint of its significance in cholinergic modulation of the synaptic transmission in the CA1 field of the rat hippocampal slices. Microionphoretic application of ACh as well as addition of either carbachol or tolbutamide (an inhibitor of cAMP-dependent protein kinase) blocked the transmission in synapses formed by the Schaffer collaterals and commissural fibres with dendrites of carbacholine both the number of releasing quanta of the neurotransmitter and the probability of their release decreased. Atropine eliminated the inhibitory effect of carbacholine on synaptic transmission. Dibutyryl cAMP and forskolin increased the amplitude of synaptic potentials and completely or partially prevented the inhibitory effect of cholinomimetics on synaptic potentials. The results obtained revealed opposite effects of cholinomimetics and activators of the adenylate cyclase system on neurotransmission in synapses formed by the Schaffer collaterals/commissural fibres and dendrites of pyramidal neurons of the hippocampal CA1 field.
...
PMID:[The role of the adenyl cyclase system in cholinergic modulation of synaptic transmission in the hippocampus]. 257 80

In situ hybridization was used to localize cAMP-dependent protein kinase (PKA) mRNAs in the adult mouse CNS. The PKA holoenzyme contains two catalytic (C) subunits and a regulatory (R) subunit dimer. Our studies demonstrate expression of two isoforms of C (C alpha and C beta) and four isoforms of R (RI alpha, RI beta, RII alpha, and RII beta) in the CNS. mRNAs for C alpha, RI alpha, and RI beta preferentially localize in the neocortex, caudate-putamen, hypothalamus, thalamus, and hippocampus. Hybridization with C beta and RII beta probes is clearly distinguished from the C alpha-like pattern by a reduced level of hybridization in the thalamus and by a relative increase in expression in the dentate gyrus compared with cell layers CA1-3 in the hippocampus. RII alpha transcripts are very specifically localized in the medial habenula. The differential expression of PKA subunit genes suggests that functional differences in cAMP responses within neural tissues may be mediated by the biochemical properties of specific PKA isoforms.
...
PMID:Distinct patterns of cAMP-dependent protein kinase gene expression in mouse brain. 261 96

The role of the Ca2+/phospholipid-dependent, diacylglycerol-activated enzyme protein kinase C (PKC) in rabbit eyelid conditioning was examined. PKC was partially purified from the CA1 region of hippocampal slices from naive, pseudoconditioned, and conditioned rabbits 24 hr after the rabbits were well conditioned. Crude membrane and cytosol fractions were prepared. In conditioned rabbits, significantly more PKC activity (63.3%) was associated with the membrane fraction (and significantly less with the cytosol fraction) compared to naive (42.0%) and pseudoconditioned (44.7%) animals. These differences in distribution of enzyme activity were paralleled by differences in stimulation of enzyme activity by Ca2+, phospholipid, and diacylglycerol. There were no between-group differences in basal protein kinase activity. These results suggest that there is a long-term translocation of PKC from cytosol to membrane as a result of conditioning. Autoradiographic binding of radioactive phorbol 12,13-dibutyrate to PKC demonstrated that almost all specific binding was in the stratum radiatum, a region containing the proximal apical dendrites of CA1 pyramidal neurons. Therefore, this may be the site of the conditioning-specific PKC translocation, a locus well-suited to underlie the biophysical effects of conditioning.
...
PMID:Classical conditioning induces long-term translocation of protein kinase C in rabbit hippocampal CA1 cells. 316 20

Long-term potentiation (LTP) in the hippocampus is an interesting example of synaptic plasticity because of its induction by physiological discharge rates and its long duration. Of the possible biochemical mechanisms that regulate prolonged changes in cell function, protein phosphorylation is a particularly attractive candidate. We have therefore examined the effect of intracellular injection of calcium/diacylglycerol-dependent protein kinase (protein kinase C (PKC] in CA1 pyramidal neurones in hippocampal slices. Injection of the active enzyme elicited long-lasting enhancement of synaptic transmission, similar to LTP, whereas inactivated kinase failed to do so. The observed changes included an increased amplitude of the excitatory post-synaptic potential (e.p.s.p.) and an increased probability of firing and a reduced latency of the associated actin potential.
...
PMID:Protein kinase C injection into hippocampal pyramidal cells elicits features of long term potentiation. 361 46

Injection of small volumes of N-methyl-D-aspartate (NMDA) or Sin-1 molsidomine (a nitric oxide releasing agent) onto the dendrites of granule cells in the hippocampal dentate gyrus leads to changes in the level of expression of a number of genes. There is a fall in prodynorphin mRNA levels with a corresponding increase in proenkephalin mRNA levels. Similar changes in opioid gene expression occur following the induction of long-term potentiation (LTP). We report here that at short time periods (1-6 h) after injections of NMDA or sin-1 molsidomine, there is an increase in the levels of the mRNA encoding the alpha subunit of Ca2+/calmodulin-dependent protein kinase II (CaMKII alpha), consistent with a report of elevated CaMKII alpha mRNA in postsynaptic neurons in the CA1 region of the hippocampus following LTP induction [54]. However, we also report that 24 h after injection of NMDA or sin-1, there is a dramatic decrease in CaMKII alpha mRNA levels in the vicinity of the injection. This effect is specific for CaMKII alpha mRNA, in that many other mRNA species are not affected, and occurs in the dendritic population of CaMKII alpha mRNA as well as in the pool of mRNA in the granule cell bodies. The effect is blocked by an inhibitor of cGMP-dependent protein kinase. The biphasic regulation of CaMKII alpha mRNA may be of considerable functional importance for the long-term response of granule cells to local stimulation of NMDA receptors or NO release.
...
PMID:N-methyl-D-aspartate and nitric oxide regulate the expression of calcium/calmodulin-dependent kinase II in the hippocampal dentate gyrus. 747 22


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---