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Dock7
Dedicator of cytokinesis protein (Dock7) is a large (~240 kDa) protein encoded in the human by the ''DOCK7'' gene, involved in intracellular signalling networks. It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G-proteins. Dock7 activates isoforms of the small G protein Rac. Discovery Dock7 was identified as one of a number of proteins which share high sequence similarity with the previously described protein Dock180, the archetypal member of the DOCK family. Dock7 expression has been reported in neurons and in the HEK 293 cell line. Structure and function Dock7 is part of a large class of proteins (GEFs) which contribute to cellular signalling events by activating small G proteins. In their resting state G proteins are bound to Guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphosphate (GTP). GEFs activate G proteins b ...
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DOCK (protein)
DOCK (Dedicator of cytokinesis) is a family of related proteins involved in intracellular signalling networks. DOCK family members contain a RhoGEF domain to function as guanine nucleotide exchange factors to promote GDP release and GTP binding to specific Small GTPases of the Rho family (e.g., Rac and Cdc42), leading to their activation since Rho proteins are inactive when bound to GDP but active when bound to GTP. DOCK family proteins are categorised into four subfamilies based on their sequence homology: *DOCK-A subfamily **Dock180 (also known as Dock1) **Dock2 ** Dock5 *DOCK-B subfamily ** Dock3 (also known as MOCA and PBP) ** Dock4 *DOCK-C subfamily (also known as Zir subfamily) **Dock6 (also known as Zir1) ** Dock7 (also known as Zir2) ** Dock8 (also known as Zir3) *DOCK-D subfamily (also known as Zizimin subfamily) **Dock9 (also known as Zizimin1) ** Dock10 (also known as Zizimin3) **Dock11 Dock11 (Dedicator of cytokinesis), also known as Zizimin2, is a large (~240 kDa ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ...
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Dock6
Dock6 (Dedicator of cytokinesis 6), also known as Zir1 is a large (~200 kDa) protein involved in intracellular signalling networks. It is a member of the DOCK-C subfamily of the DOCK family of guanine nucleotide exchange factors which function as activators of small G proteins. Discovery Dock6 was identified as one of a family of proteins which share high sequence similarity with Dock180 Dock180, (Dedicator of cytokinesis) also known as DOCK1, is a large (~180 kDa) protein involved in intracellular signalling networks. It is the mammalian ortholog of the ''C. elegans'' protein CED-5 and belongs to the DOCK family of Guanine nucl ..., the archetypal member of the DOCK family. It has a similar domain arrangement to other DOCK proteins, with a DHR1 domain known in other proteins to bind phospholipids, and a DHR2 domain containing the GEF activity. Function There is currently very little information about the cellular role of this protein. However, Dock6 has been reporte ...
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Myelin
Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be likened to an electrical wire (the axon) with insulating material (myelin) around it. However, unlike the plastic covering on an electrical wire, myelin does not form a single long sheath over the entire length of the axon. Rather, myelin sheaths the nerve in segments: in general, each axon is encased with multiple long myelinated sections with short gaps in between called nodes of Ranvier. Myelin is formed in the central nervous system (CNS; brain, spinal cord and optic nerve) by glial cells called oligodendrocytes and in the peripheral nervous system (PNS) by glial cells called Schwann cells. In the CNS, axons carry electrical signals from one nerve cell body to another. In the PNS, axons carry signals to muscles and glands or from senso ...
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Schwann Cell
Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory ensheathing cells, enteric glia and glia that reside at sensory nerve endings, such as the Pacinian corpuscle. The two types of Schwann cells are myelinating and nonmyelinating. Myelinating Schwann cells wrap around axons of motor and sensory neurons to form the myelin sheath. The Schwann cell promoter is present in the downstream region of the human dystrophin gene that gives shortened transcript that are again synthesized in a tissue-specific manner. During the development of the PNS, the regulatory mechanisms of myelination are controlled by feedforward interaction of specific genes, influencing transcriptional cascades and shaping the morphology of the myelinated nerve fibers. Schwann cells are involved in many important aspects of peri ...
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Axon
An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons (pseudounipolar neurons), such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the periphery to the cell body and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction can be the cause of many inherited and acquired neurological disorders that affect both the peripheral and central neurons. Nerve fibers are classed into three typesgroup A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated, and group C are unmyelinated. ...
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Neurite
A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because it can be difficult to tell axons from dendrites before differentiation is complete. Neurite development The development of a neurite requires a complex interplay of both extracellular and intracellular signals. At every given point along a developing neurite, there are receptors detecting both positive and negative growth cues from every direction in the surrounding space. The developing neurite sums together all of these growth signals in order to determine which direction the neurite will ultimately grow towards. While not all of the growth signals are known, several have been identified and characterized. Among the known extracellular growth signals are netrin, a midline chemoattractant, and semaphorin, ephrin and collaps ...
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Hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, and plays important roles in the consolidation of information from short-term memory to long-term memory, and in spatial memory that enables navigation. The hippocampus is located in the allocortex, with neural projections into the neocortex in humans, as well as primates. The hippocampus, as the medial pallium, is a structure found in all vertebrates. In humans, it contains two main interlocking parts: the hippocampus proper (also called ''Ammon's horn''), and the dentate gyrus. In Alzheimer's disease (and other forms of dementia), the hippocampus is one of the first regions of the brain to suffer damage; short-term memory loss and disorientation are included among the early symptoms. Damage to the hippocampus can also result from ...
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LY294002
LY294002 is a morpholine-containing chemical compound that is a potent inhibitor of numerous proteins, and a strong inhibitor of phosphoinositide 3-kinases (PI3Ks). It is generally considered a non-selective research tool, and should not be used for experiments aiming to target PI3K uniquely. Two of these are the proto-oncogene serine/threonine-protein kinase (PIM1) and the phosphatidylinositol-4,5-bisphosphate 3-kinase P110 gamma, catalytic subunit gamma isoform. With an IC50 of 1.4 μM it is somewhat less potent than wortmannin, another well-known PI3 kinase inhibitor. However, LY294002 is a reversible inhibitor of PI3K whereas wortmannin acts irreversibly. Application of LY294002 causes a substantial acceleration of MEPP frequency (150 μM) at the frog neuromuscular junction through a mechanism that is independent of intraterminal calcium. LY294002 causes the release of MEPPs through a perturbation of synaptotagmin function. LY294002 is also a BET inhibitor (e.g. of BRD2, ...
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Phosphoinositide 3-kinase
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 ha ...
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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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