Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prefrontal cortex is involved in the integration and interpretation of information for directing thoughts and planning action. Working memory is defined as the active maintenance of information in mind and is thought to lie at the core of many prefrontal functions. Although dopamine and other neurotransmitters have been implicated, the intracellular events activated by their receptors that influence working memory are poorly understood. We demonstrate that working memory involves transient changes in prefrontal G(q/11)-signaling and in calcium-dependent intracellular protein phosphatase and kinase activity. Interestingly, inhibition of the calcium activated phosphatase calcineurin impaired, while calcium/calmodulin dependent kinase II (CaMKII) and calcium-dependent protein kinase C (PKC) enhanced, working memory. Our findings suggest that the active maintenance of information required for working memory involves transient changes in the balance of these enzymes' activities.
Learn Mem
PMID:A role for prefrontal calcium-sensitive protein phosphatase and kinase activities in working memory. 1580 9

The isoforms of cAMP-dependent protein kinase (PKA) show distinct biochemical properties and subcellular localization, suggesting different physiological functions, and conferring the fine-tuning between the activation of cAMP-PKA cascade and the cellular response. The critical role of PKA in memory and synaptic plasticity has been extensively demonstrated both in vertebrates and invertebrates, but the role of PKA isoforms is a matter of debate. Here we present experimental data showing differential PKA activation profiles after two different experiences: an instance of associative contextual learning (context-signal learning) and a single exposure to a novel context, both in the learning and memory model of the crab Chasmagnathus. Differences were found in the temporal course of activation and in the involvement of PKA isoforms. We found increased PKA activity immediately and 6 h after context-signal training correlating with the critical periods during which pharmacological inhibition of PKA disrupts memory formation. In contrast, PKA activity increased immediately but not 6 h after single exposure to a novel context. The amounts of PKA I and PKA II holoenzymes were analyzed to determine changes in holoenzyme levels and/or differential activation induced by both experiences. Results indicate that context-induced PKA activation is at least in part due to PKA II, and that PKA activation 6 h after context-signal learning coincides with an increase in the total level of PKA I. Considering the higher sensitivity of PKA I to cAMP, its increment can account for the PKA activation found 6 h after training and is proposed as a novel mechanism providing the prolonged PKA activation during memory consolidation.
Neurobiol Learn Mem 2005 May
PMID:Differential activity profile of cAMP-dependent protein kinase isoforms during long-term memory consolidation in the crab Chasmagnathus. 1582 Aug 59

The prefrontal cortex (PFC) is known to actively hold information "online" for a period of seconds in working memory for guiding goal-directed behavior. It has been proposed that relevant information is stored in other brain regions, which is retrieved and held in working memory for subsequent assimilation by the PFC in order to guide behavior. It is uncertain whether PFC stores information outside the temporal limits of working memory. Here, we demonstrate that although enhanced cAMP-dependent protein kinase A (PKA) activity in the PFC is detrimental to working memory, it is required for performance in tasks involving conflicting representations when memory storage is needed for minutes. This study indicates that distinct molecular mechanisms within the PFC underlie information storage for seconds (working memory) and for minutes (short-term memory). In addition, our results demonstrate that short-term memory storage within the prefrontal cortex is required for guiding behavior in tasks with conflicts and provides a plausible mechanism by which the prefrontal cortex executes cognitive control.
Learn Mem
PMID:Distinct prefrontal molecular mechanisms for information storage lasting seconds versus minutes. 1593 May 1

In area CA1 of hippocampal slices which are allowed to recover from slicing "in interface" and where recordings are carried out in interface, a single 1-sec train of 100-Hz stimulation triggers a short-lasting long-term potentiation (S-LTP), which lasts 1-2 h, whereas multiple 1-sec trains induce a long-lasting LTP (L-LTP), which lasts several hours. Moreover, the threshold and the features of these LTP depend on the history of the neurons, a phenomenon known as metaplasticity. Here, where all recordings were performed in interface, we found that allowing the slices to recover "in submersion" had dramatic metaplastic effects. In these conditions, a single 1-sec train at 100 Hz induced an L-LTP which lasted at least 4 h and was dependent on protein synthesis. Interestingly, this type of metaplasticity was observed when the concentration of Mg(++) used was 1.0 mM but not when it was 1.3 mM. The LTP induced by four 1-sec trains at 100 Hz was similar whatever the incubation method. However, the signaling cascades recruited to achieve that pattern were different. In the interface-interface paradigm (recovery and recording both in interface) the four-train induced LTP recruited the PKA signaling pathway but not that of the p42/44MAPK. On the contrary, in the submersion-interface paradigm the four-train induced LTP recruited the p42/44MAPK signaling pathway but not that of the PKA. To our knowledge this is the first example of metaplasticity involving the recruitment of signaling cascades in LTP.
Learn Mem
PMID:The characteristics of LTP induced in hippocampal slices are dependent on slice-recovery conditions. 1670 33

The cAMP/PKA pathway plays a critical role in learning and memory systems in animals ranging from mice to Drosophila to Aplysia. Studies of olfactory learning in Drosophila suggest that altered expression of either positive or negative regulators of the cAMP/PKA signaling pathway beyond a certain optimum range may be deleterious. Here we provide genetic evidence of the behavioral and physiological effects of increased signaling through the cAMP/PKA pathway in mice. We have generated transgenic mice in which the expression of a constitutively active form of Gsalpha (Gsalpha* Q227L), the G protein that stimulates adenylyl cyclase activity, is driven in neurons within the forebrain by the promoter from the CaMKIIalpha gene. Despite significantly increased adenylyl cyclase activity, Gsalpha* transgenic mice exhibit PKA-dependent decreases in levels of cAMP due to a compensatory up-regulation in phosphodiesterase activity. Interestingly, Gsalpha* transgenic mice also exhibit enhanced basal synaptic transmission. Consistent with a role for the cAMP/PKA pathway in learning and memory, Gsalpha* transgenic mice show impairments in spatial learning in the Morris water maze and in contextual and cued fear conditioning tasks. The learning deficits observed in these transgenic mice suggest that associative and spatial learning requires regulated Gsalpha protein signaling, much as does olfactory learning in Drosophila.
Learn Mem
PMID:Chronically increased Gsalpha signaling disrupts associative and spatial learning. 1714 4

A-kinase anchoring protein 150 (AKAP150) is a multi-enzyme signaling complex that coordinates the action of PKA, PKC, and PP2B at neuronal membranes and synapses. We measured levels of AKAP150 protein in the hippocampus 6h after training mice in a contextual fear conditioning paradigm. In contextual fear conditioning mice learn to associate a context with a footshock presentation. Mice were divided in four experimental groups with different training protocols: naive, no footshock exposure, immediate footshock exposure, and footshock 3min after exposure to the context. We found that AKAP150 protein levels were increased upon exposing mice to the novel context independent of the training protocol. However, when the animals were habituated to the experimental context, only mice that learned to associate the context with the footshock showed an upregulation of AKAP150. We suggest that upregulated levels of AKAP150 contribute to processing the exposure to a novel context and associative learning.
Neurobiol Learn Mem 2007 May
PMID:Both exposure to a novel context and associative learning induce an upregulation of AKAP150 protein in mouse hippocampus. 1727 Apr 71

In a previous study, the Schistosoma mansoni Rho1 protein was able to complement Rho1 null mutant Saccharomyces cerevisiae cells at restrictive temperatures and under osmotic stress (low calcium concentration) better than the human homologue (RhoA). It is known that under osmotic stress, the S. cerevisiae Rho1 triggers two distinct pathways: activation of the membrane 1,3-beta-glucan synthase enzymatic complex and activation of the protein kinase C1 signal transduction pathway, promoting the transcription of response genes. In the present work the SmRho1 protein and its mutants smrho1E97P, smrho1L101T, and smrho1E97P, L101T were used to try to clarify the basis for the differential complementation of Rho1 knockout yeast strain by the human and S. mansoni genes. Experiments of functional complementation in the presence of caffeine and in the presence of the osmotic regulator sorbitol were conducted. SmRho1 and its mutants showed a differential complementation of the yeast cells in the presence of caffeine, since smrho1E97P and smrho1E97P, L101T mutants showed a delay in the growth when compared to the yeast complemented with the wild type SmRho1. However, in the presence of sorbitol and caffeine the wild type SmRho1 and mutants showed a similar complementation phenotype, as they allowed yeast growth in all caffeine concentrations tested.
Mem Inst Oswaldo Cruz 2006 Sep
PMID:Functional complementation of a yeast knockout strain by Schistosoma mansoni Rho1 GTPase in the presence of caffeine, an agent that affects mutants defective in the protein kinase C signal transduction pathway. 1730 90

Animals must be able to find and evaluate food to ensure survival. The ability to associate a cue with the presence of food is advantageous because it allows an animal to quickly identify a situation associated with a good, bad, or even harmful food. Identifying genes underlying these natural learned responses is essential to understanding this ability. Here, we investigate whether natural variation in the foraging (for) gene in Drosophila melanogaster larvae is important in mediating associations between either an odor or a light stimulus and food reward. We found that for influences olfactory conditioning and that the mushroom bodies play a role in this for-mediated olfactory learning. Genotypes associated with high activity of the product of for, cGMP-dependent protein kinase (PKG), showed greater memory acquisition and retention compared with genotypes associated with low activity of PKG when trained with three conditioning trials. Interestingly, increasing the number of training trials resulted in decreased memory retention only in genotypes associated with high PKG activity. The difference in the dynamics of memory acquisition and retention between variants of for suggests that the ability to learn and retain an association may be linked to the foraging strategies of the two variants.
Learn Mem 2007 May
PMID:Natural variation in Drosophila larval reward learning and memory due to a cGMP-dependent protein kinase. 1752 25

Latent inhibition is a phenomenon by which pre-exposure to a conditioned-stimulus (CS), prior to subsequent pairings of that same CS with an unconditioned-stimulus (US), results in decreased conditioned responding to the CS. Previous work in our laboratory has suggested that the entorhinal cortex is critically involved in the establishment of latent inhibition of cued fear conditioning. Furthermore, utilizing systemic pharmacology, we have demonstrated a role for of NMDA receptors, protein kinase A (PKA), and mitogen activated protein kinase (MAPK, also known as ERK) in latent inhibition of cued fear conditioning, but until now, where these cell signaling cascades are critically activated during latent inhibition of cued fear was unknown. Here, we use direct drug infusion to demonstrate that cell signaling via NMDA receptors, the cAMP/PKA pathway, and the MAPK pathway within the entorhinal cortex are critically involved in latent inhibition of cued fear conditioning. In the present study, CS pre-exposed mice received 20 CS pre-exposures 24h prior to two pairings of the same CS with a 0.53 mA foot shock US, while control animals receive no pre-exposure to the CS. The NMDA antagonist APV (0.25 or 2.5 microg/side), the cAMP inhibitor Rp-cAMP (1.8 or 18.0 microg/side), or the MAPK inhibitor U0126 (0.1 or 1.0 microg/side) were directly infused into the entorhinal cortex prior to pre-exposure. All three drugs produced dose-dependent disruptions in latent inhibition of cued fear conditioning. Importantly, none of the drugs had any effect on cued fear conditioning when administered on training day, suggesting that the effects of each of the drugs were specific to CS pre-exposure. These results are discussed in relation to the potential mechanisms of plasticity that support latent inhibition of cued fear conditioning.
Neurobiol Learn Mem 2007 Oct
PMID:Signal transduction mechanisms within the entorhinal cortex that support latent inhibition of cued fear conditioning. 1756 Aug 14

Activity-dependent changes in synaptic efficacy are thought to be the key cellular mechanism for the formation and storage of both explicit and implicit memory. Different patterns of stimulation can elicit different changes in the efficiency on excitatory synaptic transmission. Here, we examined the synaptic changes in the amygdala of adult mice produced by low-frequency stimulation (1 Hz, 15 min, LFS). We first compared the synaptic changes induced by LFS in three different synaptic pathways of amygdala: cortical-lateral amygdala, thalamic-lateral amygdala, and lateral-basolateral amygdala pathways. We find that the plastic changes induced by LFS are different between synaptic pathways. Low-frequency stimulation selectively elicits a slow onset and protein synthesis-dependent late-phase LTP in the cortical-lateral amygdala pathway, but not in the thalamic-lateral or lateral-basolateral pathways. We next analyzed LTP induced by LFS in the cortical-lateral amygdala pathway and found that three PKA-coupling neurotransmitter receptors are involved: 5-HT4, Dopamine D1, and beta-adrenergic receptors. Antagonists of these receptors block the LFS L-LTP, but the effects of agonists of these receptors are clearly different. These results indicate that the threshold for the induction of LFS L-LTP is different among these pathways and that the maintenance of LFS L-LTP requires a cross-talk among multiple neurotransmitters.
Learn Mem 2007 Jul
PMID:Low-frequency stimulation induces a pathway-specific late phase of LTP in the amygdala that is mediated by PKA and dependent on protein synthesis. 1762 8


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