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Phosphatidylinositol (3,4,5)-trisphosphate
Phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)''P''3), abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP2). It is a phospholipid that resides on the plasma membrane. Discovery In 1988, Lewis C. Cantley published a paper describing the discovery of a novel type of phosphoinositide kinase with the unprecedented ability to phosphorylate the 3' position of the inositol ring resulting in the formation of phosphatidylinositol-3-phosphate (PI3P). Working independently, Alexis Traynor-Kaplan and coworkers published a paper demonstrating that a novel lipid, phosphatidylinositol 3,4,5 trisphosphate (PIP3) occurs naturally in human neutrophils with levels that increased rapidly following physiologic stimulation with chemotactic peptide. Subsequent studies demonstrated that ''in vivo'' the enzyme originally identified by Cantley's group prefers PtdIns(4,5)P2 as a substrate, pr ...
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Phosphoinositide 3-kinases
Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. PI3Ks are a family of related intracellular signal transducer enzymes capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol (PtdIns). The pathway, with oncogene PIK3CA and tumor suppressor gene PTEN, is implicated in the sensitivity of cancer tumors to insulin and IGF1, and in calorie restriction. Discovery The discovery of PI3Ks by Lewis Cantley and colleagues began with their identification of a previously unknown phosphoinositide kinase associated with the polyoma middle T protein. They observed unique substrate specificity and chromatographic properties of the products of the lipid kinase, leading to the discovery that this phosphoinositide kinase had ...
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Phosphatidylinositol (3,4)-bisphosphate
Phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)''P''2) is a minor phospholipid component of cell membranes, yet an important second messenger. The generation of PtdIns(3,4)''P''2 at the plasma membrane activates a number of important cell signaling pathways. Of all the phospholipids found within the membrane, inositol phospholipids make up less than 10%. Phosphoinositide’s (PI’s) also known as phosphatidylinositol phosphates, are synthesized in the cells endoplasmic reticulum by the protein phosphatidylinositol synthase (PIS). PI’s are highly compartmentalized, their main components include a glycerol backbone, two fatty acid chains enriched with stearic acid and arachidonic acid, and an inositol ring whose phosphate groups regulation differs between organelles depending on the specific PI and PIP kinases and PIP phosphatases present in the organelle (Image 1). These kinases and phosphatases conduct phosphorylation and dephosphorylation at the inositol sugar head groups ...
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Synaptic Plasticity
In neuroscience, synaptic plasticity is the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity. Since memories are postulated to be represented by vastly interconnected neural circuits in the brain, synaptic plasticity is one of the important neurochemical foundations of learning and memory (''see Hebbian theory''). Plastic change often results from the alteration of the number of neurotransmitter receptors located on a synapse. There are several underlying mechanisms that cooperate to achieve synaptic plasticity, including changes in the quantity of neurotransmitters released into a synapse and changes in how effectively cells respond to those neurotransmitters. Synaptic plasticity in both excitatory and inhibitory synapses has been found to be dependent upon postsynaptic calcium release. Historical discoveries In 1973, Terje Lømo and Tim Bliss first described the now widely studied phenomenon of long-term pote ...
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Synaptic Depression
Synaptic may refer to: * Synapse, part of the nervous system * Synaptic (software), a Linux graphical package management program * Synaptics, a semiconductor manufacturer * ''Synaptics'' (Mouse on Mars EP), 2017 See also * Synapse (other) * Synapsis Synapsis is the pairing of two chromosomes that occurs during meiosis. It allows matching-up of homologous pairs prior to their segregation, and possible chromosomal crossover between them. Synapsis takes place during prophase I of meiosis. Whe ...
, the pairing of two homologous chromosomes {{disambig ...
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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 ...
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AMPA Expression
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 ...
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ARNO
The Arno is a river in the Tuscany region of Italy. It is the most important river of central Italy after the Tiber. Source and route The river originates on Monte Falterona in the Casentino area of the Apennines, and initially takes a southward curve. The river turns to the west near Arezzo passing through Florence, Empoli and Pisa, flowing into the Tyrrhenian Sea at Marina di Pisa. With a length of , it is the largest river in the region. It has many tributaries: Sieve at long, Bisenzio at , Ombrone Pistoiese at , and the Era, Elsa, Pesa, and Pescia. The drainage basin amounts to more than and drains the waters of the following subbasins: *The Casentino, in the province of Arezzo, formed by the upper course of the river until its confluence with the Maestro della Chiana channel. *The Val di Chiana, a plain drained in the 18th century, which until then had been a marshy area tributary of the Tiber. *The upper Valdarno, a long valley bordered on the east by th ...
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Bruton's Tyrosine Kinase
Bruton's tyrosine kinase (abbreviated Btk or BTK), also known as tyrosine-protein kinase BTK, is a tyrosine kinase that is encoded by the ''BTK'' gene in humans. BTK plays a crucial role in B cell development. Structure BTK contains five different protein interaction domains. These domains include an amino terminal pleckstrin homology (PH) domain, a proline-rich TEC homology (TH) domain, SRC homology (SH) domains SH2 and SH3, as well as a kinase domain with enzymatic activity. Function BTK plays a crucial role in B cell development as it is required for transmitting signals from the pre-B cell receptor that forms after successful immunoglobulin heavy chain rearrangement. It also has a role in mast cell activation through the high-affinity IgE receptor. Btk contains a PH domain that binds phosphatidylinositol (3,4,5)-trisphosphate (PIP3). PIP3 binding induces Btk to phosphorylate phospholipase C, which in turn hydrolyzes PIP2, a phosphatidylinositol, into two second mess ...
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Phosphoinositide-dependent Kinase-1
In the field of biochemistry, PDPK1 refers to the protein 3-phosphoinositide-dependent protein kinase-1, an enzyme which is encoded by the ''PDPK1'' gene in humans. It is implicated in the development and progression of melanomas. Function PDPK1 is a master kinase, which is crucial for the activation of AKT/PKB and many other AGC kinases including PKC, S6K, SGK. An important role for PDPK1 is in the signalling pathways activated by several growth factors and hormones including insulin signaling. Mice lacking PDPK1 die during early embryonic development, indicating that this enzyme is critical for transmitting the growth-promoting signals necessary for normal mammalian development. Mice that are deficient in PDPK1 have a ≈40% decrease in body mass, mild glucose intolerance, and are resistant to cancer brought about by hyperactivation of the PI3K pathway (PTEN+/-). Plant PDK1 plays an important role in regulating PIN-mediated auxin transport, and is thus involved in v ...
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PH Domain
In chemistry, pH (), historically denoting "potential of hydrogen" (or "power of hydrogen"), is a scale used to specify the acidity or basicity of an aqueous solution. Acidic solutions (solutions with higher concentrations of ions) are measured to have lower pH values than basic or alkaline solutions. The pH scale is logarithmic and inversely indicates the concentration of hydrogen ions in the solution.Bates, Roger G. ''Determination of pH: theory and practice''. Wiley, 1973. :\ce = - \log(a_\ce) = -\log( ce\ce M) where M = mol dm−3. At 25 °C (77 °F), solutions with a pH less than 7 are acidic, and solutions with a pH greater than 7 are basic. Solutions with a pH of 7 at this temperature are neutral (i.e. have the same concentration of H+ ions as OH− ions, i.e. pure water). The neutral value of the pH depends on the temperaturebeing lower than 7 if the temperature increases above 25 °C. The pH value can be less than 0 for very concentrated strong acids, ...
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Inositol
Inositol, or more precisely ''myo''-inositol, is a carbocyclic sugar that is abundant in the brain and other mammalian tissues; it mediates cell signal transduction in response to a variety of hormones, neurotransmitters, and growth factors and participates in osmoregulation. It is a sugar alcohol with half the sweetness of sucrose (table sugar). It is made naturally in the human body from glucose. A human kidney makes about two grams per day. Other tissues synthesize it too, and the highest concentration is in the brain, where it plays an important role by making other neurotransmitters and some steroid hormones bind to their receptors. Inositol is promoted as a dietary supplement in the management of polycystic ovary syndrome (PCOS). However, there is only evidence of very low quality for its efficacy in increasing fertility for IVF in women with PCOS. Overview ''myo''-Inositol plays an important role as the structural basis for a number of secondary messengers in eukaryotic ...
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Phosphatidylinositol (4,5)-bisphosphate
Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins. PIP2 also forms lipid clusters that sort proteins. PIP2 is formed primarily by the type I phosphatidylinositol 4-phosphate 5-kinases from PI(4)P. In metazoans, PIP2 can also be formed by type II phosphatidylinositol 5-phosphate 4-kinases from PI(5)P. The fatty acids of PIP2 are variable in different species and tissues, but the most common fatty acids are stearic in position 1 and arachidonic in 2. Signaling pathways PIP2 is a part of many cellular signaling pathways, including PIP2 cycle, PI3K signalling, and PI5P metabolism. Recently, it has been found in the nucleus with unknown function. Functions Cytoskeleton dynamics near membranes PIP2 regulates the organization, polymerization, and bran ...
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