CAMKII
/calmodulin-dependent protein kinase II (CaM kinase II or CaMKII) is a serine/threonine-specific protein kinase that is regulated by the / calmodulin complex. CaMKII is involved in many signaling cascades and is thought to be an important mediator of learning and memory. CaMKII is also necessary for homeostasis and reuptake in cardiomyocytes, chloride transport in epithelia, positive T-cell selection, and CD8 T-cell activation. Misregulation of CaMKII is linked to Alzheimer's disease, Angelman syndrome, and heart arrhythmia. Types There are two types of CaM kinase: * Specialized CaM kinases, such as the myosin light chain kinase that phosphorylates myosin, causing smooth muscles to contract * Multifunctional CaM kinases, also collectively called ''CaM kinase II'', which play a role in neurotransmitter secretion, transcription factor regulation, and glycogen metabolism. Structure, function, and autoregulation CaMKII accounts for 1–2% of all proteins in the brain ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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CAMK2A
Calcium/calmodulin-dependent protein kinase type II subunit alpha (CAMKIIα), protein kinase , is one subunit of CamKII, a protein kinase (i.e., an enzyme which phosphorylates proteins) that in humans is encoded by the ''CAMK2A'' gene. Function The product of the CAMK2A gene is an enzyme that belongs to the serine/threonine-specific protein kinase family, as well as the Ca2+/calmodulin-dependent protein kinase II subfamily. Ca2+ signaling is crucial for several aspects of synaptic plasticity at glutamatergic synapses. This enzyme is composed of four different chains: alpha, beta, gamma, and delta. The alpha chain encoded by this gene is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)-dependent activity, this protein can undergo autophosphorylation, resulting in CaM-independent activity. Two transcript variants encoding distinct isoforms have been identified for this gene. According to a 2018 study by Bru ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Camkii Kinase Domain
/calmodulin-dependent protein kinase II (CaM kinase II or CaMKII) is a serine/threonine-specific protein kinase that is regulated by the /calmodulin complex. CaMKII is involved in many signaling cascades and is thought to be an important mediator of learning and memory. CaMKII is also necessary for homeostasis and reuptake in cardiomyocytes, chloride transport in epithelia, positive T-cell selection, and CD8 T-cell activation. Misregulation of CaMKII is linked to Alzheimer's disease, Angelman syndrome, and heart arrhythmia. Types There are two types of CaM kinase: * Specialized CaM kinases, such as the myosin light chain kinase that phosphorylates myosin, causing smooth muscles to contract * Multifunctional CaM kinases, also collectively called ''CaM kinase II'', which play a role in neurotransmitter secretion, transcription factor regulation, and glycogen metabolism. Structure, function, and autoregulation CaMKII accounts for 1–2% of all proteins in the brain, and ha ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Viral Vector
Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (''in vivo'') or in cell culture (''in vitro''). Viruses have evolved specialized molecular mechanisms to efficiently transport their genomes inside the cells they infect. Delivery of genes or other genetic material by a vector is termed transduction and the infected cells are described as transduced. Molecular biologists first harnessed this machinery in the 1970s. Paul Berg used a modified SV40 virus containing DNA from the bacteriophage λ to infect monkey kidney cells maintained in culture. In addition to their use in molecular biology research, viral vectors are used for gene therapy and the development of vaccines. Key properties of a viral vector VIRAL VECTORS are tailored to their specific applications but generally share a few key properties. *''Safety'': Although viral vectors are occasionally created from pathog ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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KN-62
KN-62 is a derivative of isoquinolinesulfonamide, it is a selective, specific and cell permeable inhibitor of Ca2+/calmodulin-dependent kinase type II (CaMK II) with IC50 of 900nM, charactered by hydrophobicity. KN-62 also potently inhibits the purinergic receptor P2X7. Inhibitory mechanism on CaMK II KN-62 blocks the combination of CaM and CaMK II by binding directly to the calmodulin binding site of the enzyme, disenables CaMK II's autophosphorylation, consequently leading inactivation. Kinetic analysis exhibits that this inhibitory effect of KN-62 is competitive with respect to calmodulin. Since KN-62 binds to the calmodulin binding site of CaMK II, KN-62 doesn't inhibit activity of autophosphorylated CaMK II. Besides, KN-62 also acts as a potent non-competitive antagonist at the purinergic receptor P2RX7 with IC50 The half maximal inhibitory concentration (IC50) is a measure of the potency of a substance in inhibiting a specific biological or biochemical function. IC50 is ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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AMPA
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate. There are several types of glutamatergic ion channels in the central nervous system including AMPA, kainic acid and ''N''-methyl-D-aspartic acid (NMDA) channels. In the synapse, these receptors serve very different purposes. AMPA can be used experimentally to distinguish the activity of one receptor from the other in order to understand their differing functions. AMPA generates fast excitatory postsynaptic potentials (EPSP). AMPA activates AMPA receptors that are non-selective cationic channels allowing the passage of Na+ and K+ and therefore have an equilibrium potential near 0 mV. AMPA was first synthesized, along with several other ibotenic acid Ibotenic acid or (''S'')-2-amino-2-(3-hydroxyisoxazol-5-yl)acetic acid, also referred to as ibotenate, is a chemical compo ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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LTP Induction
The induction of NMDA receptor-dependent long-term potentiation (LTP) in chemical synapses in the brain occurs via a fairly straightforward mechanism. A substantial and rapid rise in calcium ion concentration inside the postsynaptic cell (or more specifically, within the dendritic spine) is most possibly all that is required to induce LTP. But the mechanism of calcium delivery to the postsynaptic cell in inducing LTP is more complicated. The role of the AMPA receptor The AMPA receptor (AMPAR) is the engine that drives excitatory postsynaptic potentials (EPSPs). While some forms of the AMPAR can conduct calcium, most AMPARs found in the neocortex do not. The AMPAR, upon binding two glutamate molecules, undergoes a conformational change that resembles the opening of a clam shell. This conformational change opens an ion channel within the AMPAR protein structure that allows sodium ions to flow into the cell and potassium ions to flow out (i.e. it is a mixed cation-conducting channel). ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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NMDA Receptor
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA receptor, AMPA and kainate receptors. Depending on its subunit composition, its Ligand (biochemistry), ligands are glutamate and glycine (or D-Serine, D-serine). However, the binding of the ligands is typically not sufficient to open the channel as it may be blocked by Magnesium, Mg2+ ions which are only removed when the neuron is sufficiently depolarized. Thus, the channel acts as a “coincidence detector” and only once both of these conditions are met, the channel opens and it allows cation, positively charged ions (cations) to flow through the cell membrane. The NMDA receptor is thought to be very important for controlling synaptic plasticity and mediating learning and memory functions. The NMDA receptor is ionotropic, meaning it is a pr ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Long-term Potentiation
In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons. The opposite of LTP is long-term depression, which produces a long-lasting decrease in synaptic strength. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength. As memories are thought to be encoded by modification of synaptic strength, LTP is widely considered one of the major cellular mechanisms that underlies learning and memory. LTP was discovered in the rabbit hippocampus by Terje Lømo in 1966 and has remained a popular subject of research since. Many modern LTP studies seek to better understand its basic biology, while others aim to draw a causal link between LTP and behavioral learning. Still, others try to develop methods, pharmacologic or otherwise, of enhanc ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Autophosphorylation
Autophosphorylation is a type of post-translational modification of proteins. It is generally defined as the phosphorylation of the kinase by itself. In eukaryotes, this process occurs by the addition of a phosphate group to serine, threonine or tyrosine residues within protein kinases, normally to regulate the catalytic activity.Petsko, GA and Ringe, D 2009, 'Protein Structure and Function', Oxford University Press Inc., New York, U.S.A Autophosphorylation may occur when a kinases' own active site catalyzes the phosphorylation reaction (cis autophosphorylation), or when another kinase of the same type provides the active site that carries out the chemistry (trans autophosphorylation). The latter often occurs when kinase molecules dimerize. In general, the phosphate groups introduced are gamma phosphates from nucleoside triphosphates, most commonly ATP. Function Protein kinases, many of which are regulated by autophosphorylation, are vital in controlling the cellular prolifer ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Cell (journal)
''Cell'' is a peer-reviewed scientific journal publishing research papers across a broad range of disciplines within the life sciences. Areas covered include molecular biology, cell biology, systems biology, stem cells, developmental biology, genetics and genomics, proteomics, cancer research, immunology, neuroscience, structural biology, microbiology, virology, physiology, biophysics, and computational biology. The journal was established in 1974 by Benjamin LewinElsevier: ''Cell'': Home (accessed 12 December 2008) and is published twice monthly by , an imprint of [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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C Terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is translated from messenger RNA, it is created from N-terminus to C-terminus. The convention for writing peptide sequences is to put the C-terminal end on the right and write the sequence from N- to C-terminus. Chemistry Each amino acid has a carboxyl group and an amine group. Amino acids link to one another to form a chain by a dehydration reaction which joins the amine group of one amino acid to the carboxyl group of the next. Thus polypeptide chains have an end with an unbound carboxyl group, the C-terminus, and an end with an unbound amine group, the N-terminus. Proteins are naturally synthesized starting from the N-terminus and ending at the C-terminus. Function C-terminal retention signals While the N-terminus of a protein often conta ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License. Protein phosphorylation often activates (or deactivates) many enzymes. Glucose Phosphorylation of sugars is often the first stage in their catabolism. Phosphorylation allows cells to accumulate sugars because the phosphate group prevents the molecules from diffusing back across their transporter. Phosphorylation of glucose is a key reaction in sugar metabolism. The chemical equation for the conversion of D-glucose to D-glucose-6-phosphate in the first step of glycolysis is given by :D-glucose + ATP → D-glucose-6-phosphate + ADP : ΔG° = −16.7 kJ/mol (° indicates measurement at standard condition) Hepatic cells are freely permeable to glucose, and ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |