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

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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)

CAPL-A1 and CAPL-A2, two catalytic subunits of Aplysia cAMP-dependent protein kinase, are encoded by mRNAs generated by alternative splicing of transcripts of a gene that contains two mutually exclusive exon cassettes. The subunits are identical except for amino acids 142-183 of the 352 residues, which differ at 10 of 42 positions. CAPL-A1 and CAPL-A2 have now been expressed in insect cells and purified to homogeneity. The subunits differ in their catalytic properties, which have been determined with a series of synthetic peptide substrates. For example, kcat and Km values for the peptide LRRASLG (kemptide) are 42 s-1 and 36 microM and 28 s-1 and 17 microM for CAPL-A1 and CAPL-A2, respectively. CAPL-A1 and CAPL-A2 have different substrate specificities. For example, (kcat/Km)peptide-T/(kcat/Km)kemptide is 9.1 x 10(-3) for CAPL-A1 and 15 x 10(-3) for CAPL-A2, where peptide-T is the kemptide homologue LRRATLG. The subunits also differ in regulation as determined by their interactions with a purified type I regulatory subunit, which has an IC50 for CAPL-A1 that is 3.5 times higher than the IC50 for CAPL-A2. These modest differences reinforce accumulating evidence that the physiological state of a cell depends upon a spectrum of protein kinases with overlapping substrate specificities and regulatory properties.
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PMID:Kinetics and regulation of two catalytic subunits of cAMP-dependent protein kinase from Aplysia californica. 193 53

In both vertebrates and invertebrates, long-term memory differs from short-term in requiring protein synthesis during training. Studies of the gill and siphon withdrawal reflex in Aplysia indicate that similar requirements can be demonstrated at the level of sensory and motor neurons which may participate in memory storage. A single application of serotonin, a transmitter that mediates sensitization, to individual sensory and motor cells in dissociated cell cultures leads to enhanced transmitter release from the sensory neurons that is independent of new macromolecular synthesis. Five applications of serotonin cause a long-term enhancement, lasting one or more days, which requires translation and transcription. Prolonged application or intracellular injection into the sensory neuron of cyclic AMP, a second messenger for the action of serotonin, also produce long-term increases in synaptic strength, suggesting that some of the gene products important for long-term facilitation are cAMP-inducible. In eukaryotic cells, most cAMP-inducible genes so far studied are activated by the cAMP-dependent protein kinase (A kinase), which phosphorylates transcription factors that bind the cAMP-responsive element TGACGTCA. The cAMP-responsive element (CRE) binds a protein dimer of relative molecular mass 43,000, the CRE-binding protein (CREBP), which has been purified and shown to increase transcription when phosphorylated by the A kinase. Here we show that extracts of the Aplysia central nervous system and extracts of sensory neurons contain a set of proteins, including one with properties similar to mammalian CREBPs, that specifically bind the mammalian CRE sequence. Microinjection of the CRE sequence into the nucleus of a sensory neuron selectively blocks the serotonin-induced long-term increase in synaptic strength, without affecting short-term facilitation. Taken together, these observations suggest that one or more CREB-like transcriptional activators are required for long-term facilitation.
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PMID:Injection of the cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation. 214 68

Serotonin (5-HT) shifts the phase of the circadian oscillator of the eye of Aplysia californica in a phase dependent manner. This indicates that 5-HT acts, either directly or through some intermediaries, on a component of the oscillator. Since our goal is to identify the components of the oscillator, we are following the pathway through which 5-HT has its effect on the rhythm. The effect of 5-HT on the rhythm has been shown to be mediated by an increase in intracellular cyclic adenosine-3',5'-monophosphate (cAMP). The most likely action of cAMP is to activate cAMP-dependent protein kinase. Therefore, we used two-dimensional polyacrylamide gel electrophoresis to investigate changes in 32P labelled phosphoproteins which occur with 5-HT and other treatments. Fourteen proteins showed increased incorporation of 32P when eyes were exposed to treatments of 5-HT from CT 06 to 12. Two proteins showed decreased incorporation. 8-bt-cAMP mimicked all but one of the increases and both decreases in incorporation produced by 5-HT. 8-bt-cAMP increased incorporation into three additional proteins and decreased incorporation into three others that were not affected by 5-HT. Incorporation into one protein was increased by 5-HT but decreased by 8-bt-cAMP. By comparison, light, which has little or no effect on the rhythm at this phase, only affected one protein. The protein increased by light was also increased by 5-HT. Tetradecanoic phorbol acetate (TPA), administered during CT 06-12, also had little effect on the rhythm at this phase. TPA increased incorporation into twenty proteins and decreased incorporation into three.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in protein phosphorylation in the eye of Aplysia associated with circadian rhythm regulation by serotonin. 215 3

The ionic mechanism of the effect of intracellularly injected adenosine 3',5'-cyclic monophosphate (cAMP) on the membrane of identified neuron L5 of Aplysia kurodai was investigated with conventional voltage-clamp and ion-substitution techniques. The intracellular elevation of cAMP caused an inward current (IcAMP), which was not accompanied by a significant change in membrane conductance at potentials more hyperpolarized than -60 mV. The current increased over the voltage range (-50 to -30 mV) associated with a conductance decrease and decreased at potentials more hyperpolarized than -60 mV. Elevated intracellular cAMP was found to enhance a region of negative slope resistance in steady-state I-V relations. Duration of the IcAMP was greatly prolonged by bath-applied isobutylmethylxanthine (50 microM), but imidazole (10 mM) had an opposite effect on the IcAMP. Tolbutamide (5 mM), a protein kinase inhibitor, reduced the IcAMP. The current was not affected by the presence of bath-applied TTX (50 microM), ouabain (50 microM), or triaminopyrimidine (5 mM). Reduction of [Na+]0 reversibly decreased the IcAMP. Li+ could largely substitute for Na+. Alterations of [K+]0, and bath application of 4-AP (5 mM) and TEA (30 mM) did not affect the IcAMP. In the presence of Na+, Cl-, and divalent cations such as Ca2+ and Ba2+ inhibited the IcAMP. These results suggest that fast elevation of intracellular cAMP induces a TTX-resistant slow Na+ inward current, and the current might be due to activation of cAMP-dependent protein kinase.
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PMID:Influences of pressure-injected cyclic AMP on the membrane current and characteristics of an identified neuron of Aplysia kurodai. 242 22

The modulation of voltage-activated calcium currents by protein kinases provides excitable cells with a mechanism for regulating their electrical behaviour. At the single channel level, modulation of calcium current has, to date, been characterized only in cardiac muscle, where beta-adrenergic agonists, acting through cyclic AMP-dependent protein kinase, enhance the calcium current by increasing channel availability and opening. We now report that enhancement of calcium current in the peptidergic bag cell neurons of Aplysia by protein kinase C occurs through a different mechanism, the recruitment of a previously covert class of calcium channel. Under control conditions, bag cell neurons contain only one class of voltage-activated calcium channel with a conductance of approximately 12 pS. After exposure to agents that activate protein kinase C, these neurons also express a second class of calcium channel with a different unitary conductance (approximately 24 pS) that is never seen in untreated cells.
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PMID:Stimulation of protein kinase C recruits covert calcium channels in Aplysia bag cell neurons. 243 53

The amino acid sequences of two catalytic (C) subunits of Aplysia cAMP-dependent protein kinase (cAPK) have been deduced from the nucleotide sequences of cDNAs generated from neuronal poly(A)+ RNA. Both subunits contain 352 residues and are identical except for amino acids 142-183, which differ at 10 out of 42 positions. They derive from alternatively spliced transcripts of a single gene (CAPL) containing two mutually exclusive exon cassettes. CAPL transcripts are present in several classes of identified neurons containing transmitter-sensitive adenylate cyclase, including sensory cells, bag cells, and the left pleural giant cell. Combinatorial expression of the various regulatory (R) and C subunits might produce kinase isoforms with distinct roles in neuronal modulation. Alternatively, holoenzymes with overlapping properties together might contribute to the definition of individual cell types and physiological states.
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PMID:Two catalytic subunits of cAMP-dependent protein kinase generated by alternative RNA splicing are expressed in Aplysia neurons. 248 6

Exposure of the bag cell neurons of Aplysia to activators of protein kinase C, such as phorbol esters, enhances electrically evoked action potentials by increasing the voltage-dependent calcium current. We have hypothesized that this effect is mediated by the activation of protein kinase C (PKC). An important prediction of this hypothesis is that inhibitors of PKC should inhibit these phorbol ester-induced changes in bag cell neuronal excitability. We have now found that treatment of bag cell neurons with the protein kinase inhibitor 1-[5-isoquinolinesulfonyl]-2-methyl piperazine (H-7) inhibits the phorbol ester-induced enhancement of bag cell action potentials and prevents the enhancement of calcium current by phorbol esters. The height and width of electrically evoked action potentials in bag cell neurons can also be enhanced by cAMP analogs or agents that elevate cAMP. These agents do not influence the major voltage-dependent calcium current in the bag cell neurons but may act by modulating potassium currents and other voltage-dependent currents. We have found that microinjection of a protein inhibitor of cAMP-PK (PKA-I) into isolated bag cell neurons prevents and reverses the effect of the adenylate cyclase activator forskolin on action potentials of these cells. In contrast, H-7 does not inhibit the effects of forskolin on a variety of responses in these cells, including its effects on action potentials, granule movement, and 32P incorporation into phosphoproteins. This suggests that H-7 is selective for PKC relative to cAMP-PK in intact bag cell neurons.
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PMID:Protein kinase inhibitors selectively block phorbol ester- or forskolin-induced changes in excitability of Aplysia neurons. 253 89

1. Neurons with a receptor responded to FMRFamide (Phe-Met-Arg-Phe-NH2) were identified in the ganglion of Aplysia kurodai. Ionic mechanism and channel gating system of the FMRFamide-induced responses were investigated by current clamp and voltage clamp methods. 2. The reversal potential of FMRFamide-induced response exactly coincided with the equilibrium potential for K+. This proved that the response was produced by a specific increase in membrane permeability toward K+, exclusively. 3. The FMRFamide-induced response was not affected by the inhibitors for Ca2(+)-activated K(+)-current, i.e., TEA, apamin, and EGTA. This excluded a possibility that FMRFamide-activated K(+)-channel is a Ca2(+)-activated K(+)-channel. 4. Intracellular injection of pertussis-toxin (PTX) caused no change in either resting potential or conductance, but it irreversibly blocked the FMRFamide-induced outward current within 30 min. Similarly applied cholera toxin (CTX) showed no effect on the FMRF-amide response. 5. Intracellular application of guanosine 5'-0-(2-thiodiphosphate) (GDP beta S) caused no effect on either resting potential or conductance, but it blocked the FMRFamide-induced K(+)-current within 3 min. 6. Intracellular application of guanosine 5'-0-(3-thiotriphosphate) (GTP gamma S) alone induced a slowly developing, irreversible outward current associated with an increase in membrane conductance. However, repetitive applications of FMRFamide immediately after the start of GTP gamma S application markedly facilitated the effect of GTP gamma S on the resting membrane. 7. Intracellular application of either adenylate cyclase inhibitor (3'-deoxyadenosine) or A-kinase inhibitor (H-8) did not affect the FMRFamide-induced response. 8. It was concluded that the FMRFamide-induced K(+)-current is mediated by PTX-sensitive GTP-binding protein Gi, Go or Gk. It was also suggested that the FMRFamide-induced response is produced independently of the changes in intracellular Ca2+ or cyclic AMP.
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PMID:[The gating mechanism of K(+)-channels coupled to the FMRFamide receptor in the ganglion cells of Aplysia]. 255 80

One of the molecular mechanisms capable of regulating the physiological properties of neurones is the phosphorylation of ion channels and other cellular components by cyclic AMP-dependent protein kinase. Another protein kinase present in high concentrations in the mammalian brain is protein kinase C (a calcium/phosphatidylserine/diacylglycerol-dependent protein kinase), but there is no direct evidence, as yet, for the involvement of this enzyme in the control of neuronal excitability. We now present evidence that activation of endogenous protein kinase C by the tumour-promoting phorbol ester TPA (12-O-tetradecanoyl- phorbol-13-acetate), or intracellular injection of the purified enzyme, enhances the voltage-sensitive calcium current in bag cell neurones of the mollusc Aplysia.
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PMID:Enhancement of calcium current in Aplysia neurones by phorbol ester and protein kinase C. 257 17

Selected actions of neurotransmitters and hormones on ion channels in nerve and muscle cells are now thought to be mediated by cyclic AMP-dependent protein phosphorylation. Although the cyclic AMP-dependent protein kinase (cAMP-PK) affects the cellular properties of several neurones, its mode of action at the single-channel level has not been characterized. In addition, little is known about the identity or subcellular localization of the phosphoproteins that control channel activity and, in particular, whether the critical substrate proteins are cytoplasmic or membrane-associated. In Aplysia sensory neurones, serotonin produces a slow modulatory synaptic potential mediated by cAMP-PK that contributes to presynaptic facilitation and behavioural sensitization. Previously, we have found that serotonin acts on cell-attached membrane patches to produce prolonged all-or-none closures of a specific class of K+ channels (S channels) whose gating is weakly dependent on voltage and independent of intracellular calcium. We demonstrate here that in cell-free membrane patches from Aplysia sensory neurones, the purified catalytic subunit of cAMP-PK produces all-or-none closures of the S channel, simulating most (but not all) aspects of the action of serotonin on cell-attached patches. This result suggests that protein kinase acts on the internal surface of the membrane to phosphorylate either the channel itself or a membrane-associated protein that regulates channel activity.
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PMID:Cyclic AMP-dependent protein kinase closes the serotonin-sensitive K+ channels of Aplysia sensory neurones in cell-free membrane patches. 257 23


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