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Phosphatidylinositol 3,5-bisphosphate
Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) is one of the seven phosphoinositides found in eukaryotic cell membranes. In quiescent cells, the PtdIns(3,5)P2 levels, typically quantified by HPLC, are the lowest amongst the constitutively present phosphoinositides. They are approximately 3 to 5-fold lower as compared to PtdIns3P and PtdIns5P (Phosphatidylinositol 5-phosphate) levels, and more than 100-fold lower than the abundant PtdIns4P ( Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2. PtdIns(3,5)P2 was first reported to occur in mouse fibroblasts and budding yeast S. cerevisiae in 1997.Whiteford CC, Brearley CA, Ulug ET. Phosphatidylinositol 3,5-bisphosphate defines a novel PI 3-kinase pathway in resting mouse fibroblasts. Biochem J. 1997 May 1;323 ( Pt 3):597-601. In S. cerevisiae PtdIns(3,5)P2 levels increase dramatically during hyperosmotic shock.Dove SK, Cooke FT, Douglas MR, Sayers LG, Parker PJ, Michell RH. Osmotic stress activates phosphatidylinositol-3, ...
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VAC14
Protein VAC14 homolog, also known as ArPIKfyve (Associated Regulator of PIKfyve), is a protein that in humans is encoded by the ''VAC14'' gene. Function The content of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) in endosomal membranes changes dynamically with fission and fusion events that generate or absorb intracellular transport vesicles. The ArPIKfyve protein scaffolds a trimolecular complex to tightly regulate the level of PtdIns(3,5)P2. Other components of this complex are the PtdIns(3,5)P2-synthesizing enzyme PIKFYVE and the Sac1-domain-containing PtdIns(3,5)P2 5-phosphatase Sac3, encoded by the human gene FIG4. VAC14 functions as an activator of PIKFYVE. Studies in VAC14 knockout mice indicate that, in addition to increasing the PtdIns(3,5)P2-producing activity of PIKfyve, VAC14 also controls the steady-state levels of another rare phosphoinositide linked to PIKfyve enzyme activity – phosphatidylinositol 5-phosphate. It is seen that VAC14 is scaffold pro ...
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Platelets
Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cytoplasm from megakaryocytes which reside in bone marrow or lung tissue, and then enter the circulation. Platelets are found only in mammals, whereas in other vertebrates (e.g. birds, amphibians), thrombocytes circulate as intact mononuclear cells. One major function of platelets is to contribute to hemostasis: the process of stopping bleeding at the site where the lining of vessels (endothelium) has been interrupted. Platelets gather at the site and, unless the interruption is physically too large, they plug the hole. First, platelets attach to substances outside the interrupted endothelium: ''adhesion''. Second, they change shape, turn on receptors and secrete chemical messengers: ''activation''. Third, they connect to each other throu ...
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Protein Kinase C
In cell biology, protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins, or a member of this family. PKC enzymes in turn are activated by signals such as increases in the concentration of diacylglycerol (DAG) or calcium ions (Ca2+). Hence PKC enzymes play important roles in several signal transduction cascades. In biochemistry, the PKC family consists of fifteen isozymes in humans. They are divided into three subfamilies, based on their second messenger requirements: conventional (or classical), novel, and atypical. Conventional (c)PKCs contain the isoforms α, βI, βII, and γ. These require Ca2+, DAG, and a phospholipid such as phosphatidylserine for activation. Novel (n)PKCs include the δ, ε, η, and θ isoforms, and require DAG, but do not require Ca2+ ...
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Lymphocytes
A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), and innate lymphoid cells (ILCs; "innate T cell-like" cells involved in mucosal immunity and homeostasis), of which natural killer cells are an important subtype (which functions in cell-mediated, cytotoxic innate immunity). They are the main type of cell found in lymph, which prompted the name "lymphocyte" (with ''cyte'' meaning cell). Lymphocytes make up between 18% and 42% of circulating white blood cells. Types The three major types of lymphocyte are T cells, B cells and natural killer (NK) cells. They can also be classified as small lymphocytes and large lymphocytes based on their size and appearance. Lymphocytes can be identified by their large nucleus. T cells and B cells T cells (thymus cells) and B cells ( bone marrow- or ...
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UV Light
Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of the total electromagnetic radiation output from the Sun. It is also produced by electric arcs, Cherenkov radiation, and specialized lights, such as mercury-vapor lamps, tanning lamps, and black lights. The photons of ultraviolet have greater energy than those of visible light, from about 3.1 to 12  electron volts, around the minimum energy required to ionize atoms. Although long-wavelength ultraviolet is not considered an ionizing radiation because its photons lack sufficient energy, it can induce chemical reactions and cause many substances to glow or fluoresce. Many practical applications, including chemical and biological effects, are derived from the way that UV radiation can interact with organic molecules. These i ...
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Interleukin 2
Interleukin-2 (IL-2) is an interleukin, which is a type of cytokine signaling molecule forming part of the immune system. It is a 15.5–16 Dalton (unit), kDa protein that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity. IL-2 is part of the body's immune response, natural response to microbial infection, and in discriminating between foreign ("non-self") and "self". IL-2 mediates its effects by binding to IL-2 receptors, which are expressed by lymphocytes. The major sources of IL-2 are activated T helper cell, CD4+ T cells and activated CD8+ T cells, CD8+ T cells. Put shortly the function of IL-2 is to stimulate the growth of helper, cytotoxic and regulatory T cells. IL-2 receptor IL-2 is a member of a specific family of cytokines, each member of which has a Helix bundle#Four-helix bundles, four alpha helix bundle; this cytokine family also includes Interleukin-4, IL-4, Interleukin 7, IL-7, Interleukin 9 ...
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Fig4
Polyphosphoinositide phosphatase also known as phosphatidylinositol 3,5-bisphosphate 5-phosphatase or SAC domain-containing protein 3 (Sac3) is an enzyme that in humans is encoded by the ''FIG4'' gene. Fig4 is an abbreviation for Factor-Induced Gene. Function Sac3 protein belongs to a family of human phosphoinositide phosphatases containing a Sac1-homology domain. The Sac1 phosphatase domain encompasses approximately 400 amino acids and consists of seven conserved motifs. It harbors the signature CX5R (T/S) catalytic sequence also found in other lipid and protein tyrosine phosphatases. The founding protein, containing this evolutionarily-conserved domain, has been the first gene product isolated in a screen for Suppressors of yeast ACtin mutations and therefore named Sac1. There are 5 human genes containing a Sac1 domain. Three of these genes (gene symbols SACM1L, INPP5F and FIG4), harbor a single Sac1 domain. In the other two genes, synaptojanin 1 and 2, the Sac1 domain coexi ...
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Phosphoinositides
Phosphatidylinositol or inositol phospholipid is a biomolecule. It was initially called "inosite" when it was discovered by Léon Maquenne and Johann Joseph von Scherer in the late 19th century. It was discovered in bacteria but later also found in eukaryotes, and was found to be a signaling molecule. The biomolecule can exist in 9 different isomers. It is a lipid which contains a phosphate group, two fatty acid chains, and one inositol sugar molecule. Typically, the phosphate group has a negative charge (at physiological pH values). As a result, the molecule is amphiphilic. The production of the molecule is limited to the endoplasmic reticulum. History of phospatidylinositol Phosphatidylinositol (PI) and its derivatives have a rich history dating back to their discovery by Johann Joseph von Scherer and Léon Maquenne in the late 19th century. Initially known as " inosite" based on its sweet taste, the isolation and characterization of inositol laid the groundwork for under ...
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