Platelet-derived Growth Factor Receptor A
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Platelet-derived Growth Factor Receptor A
Platelet-derived growth factor receptor A, also termed CD140a, is a receptor located on the surface of a wide range of cell types. The protein is encoded in the human by the ''PDGFRA'' gene. This receptor binds to certain isoforms of platelet-derived growth factors (PDGFs) and thereby becomes active in stimulating cell signaling pathways that elicit responses such as cellular growth and differentiation. The receptor is critical for the embryonic development of certain tissues and organs, and for their maintenance, particularly hematologic tissues, throughout life. Mutations in ''PDGFRA'', are associated with an array of clinically significant neoplasms, notably ones of the clonal hypereosinophilia class of malignancies, as well as gastrointestinal stromal tumors (GISTs). Overall structure This gene encodes a typical receptor tyrosine kinase, which is a transmembrane protein consisting of an extracellular ligand binding domain, a transmembrane domain and an intracellular tyros ...
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Receptor (biochemistry)
In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and Signal_transduction, transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a receptor and produce physiological responses, such as a change in the electrophysiology, electrical activity of a cell. For example, GABA, an inhibitory neurotransmitter, inhibits electrical activity of neurons by binding to GABAA receptor, GABA receptors. There are three main ways the action of the receptor can be classified: relay of signal, amplification, or integration. Relaying sends the signal onward, amplification increases the effect of a single ligand (biochemistry), ligand, and integration allows the signal to be incorporated into another biochemical pathway. Receptor proteins can be classified by their location. Cell surface receptors, also known as transmembrane receptors, include ligand-gated ion channels, G prote ...
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Protein Dimer
In biochemistry, a protein dimer is a macromolecular complex or protein multimer, multimer formed by two protein monomers, or single proteins, which are usually Non-covalent interaction, non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has roots meaning "two parts", ''wikt:di-#Prefix, di-'' + ''wikt:-mer#Suffix, -mer''. A protein dimer is a type of protein quaternary structure. A protein homodimer is formed by two identical proteins while a protein heterodimer is formed by two different proteins. Most protein dimers in biochemistry are not connected by covalent bonds. An example of a non-covalent heterodimer is the enzyme reverse transcriptase, which is composed of two different amino acid chains. An exception is dimers that are linked by disulfide bridges such as the homodimeric protein IKBKG, NEMO. Some proteins contain specialized domains to ensure dimerization (dimerization domains) and specificity. The G protein- ...
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Hematopoietic Stem Cell
Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the (midgestational) aorta-gonad-mesonephros region, through a process known as endothelial-to-hematopoietic transition. In adults, haematopoiesis occurs in the red bone marrow, in the core of most bones. The red bone marrow is derived from the layer of the embryo called the mesoderm. Haematopoiesis is the process by which all mature blood cells are produced. It must balance enormous production needs (the average person produces more than 500 billion blood cells every day) with the need to regulate the number of each blood cell type in the circulation. In vertebrates, the vast majority of hematopoiesis occurs in the bone marrow and is derived from a limited number of hematopoietic stem cells that are multipotent and capable of extensive ...
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Mesoderm
The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical Embryology, 11th edition. 2010. The mesoderm forms mesenchyme, mesothelium and coelomocytes. Mesothelium lines coeloms. Mesoderm forms the muscles in a process known as myogenesis, septa (cross-wise partitions) and mesenteries (length-wise partitions); and forms part of the gonads (the rest being the gametes). Myogenesis is specifically a function of mesenchyme. The mesoderm differentiates from the rest of the embryo through intercellular signaling, after which the mesoderm is polarized by an organizing center. The position of the organizing center is in turn determined by the regions in which beta-catenin is protected from degradation by GSK-3. Beta-catenin acts as a co-factor that alters the activity of the transcription facto ...
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Thrombocytopenic
In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients and a third of surgical patients. A normal human platelet count ranges from 150,000 to 450,000 platelets/microliter (μL) of blood. Values outside this range do not necessarily indicate disease. One common definition of thrombocytopenia requiring emergency treatment is a platelet count below 50,000/μL. Thrombocytopenia can be contrasted with the conditions associated with an abnormally ''high'' level of platelets in the blood – thrombocythemia (when the cause is unknown), and thrombocytosis (when the cause is known). Signs and symptoms Thrombocytopenia usually has no symptoms and is picked up on a routine complete blood count. Some individual ...
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Mesangial Cell
Mesangial cells are specialised cells in the kidney that make up the mesangium of the glomerulus. Together with the mesangial matrix, they form the vascular pole of the renal corpuscle. The mesangial cell population accounts for approximately 30-40% of the total cells in the glomerulus. Mesangial cells can be categorized as either extraglomerular mesangial cells or intraglomerular mesangial cells, based on their relative location to the glomerulus. The extraglomerular mesangial cells are found between the afferent and efferent arterioles towards the vascular pole of the glomerulus. The extraglomerular mesangial cells are adjacent to the intraglomerular mesangial cells that are located inside the glomerulus and in between the capillaries. The primary function of mesangial cells is to remove trapped residues and aggregated protein from the basement membrane thus keeping the filter free of debris. The contractile properties of mesangial cells have been shown to be insignificant ...
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Kidney Glomeruli
The glomerulus (: glomeruli) is a network of small blood vessels (capillaries) known as a ''tuft'', located at the beginning of a nephron in the kidney. Each of the two kidneys contains about one million nephrons. The tuft is structurally supported by the mesangium (the space between the blood vessels), composed of intraglomerular mesangial cells. The blood is filtered across the capillary walls of this tuft through the glomerular filtration barrier, which yields its filtrate of water and soluble substances to a cup-like sac known as Bowman's capsule. The filtrate then enters the renal tubule of the nephron. The glomerulus receives its blood supply from an afferent arteriole of the renal arterial circulation. Unlike most capillary beds, the glomerular capillaries exit into efferent arterioles rather than venules. The resistance of the efferent arterioles causes sufficient hydrostatic pressure within the glomerulus to provide the force for ultrafiltration. The glomerulus and its ...
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Src Family Kinase
Src kinase family is a family of non-receptor tyrosine kinases that includes nine members: Src (gene), Src, YES1, Yes, FYN, Fyn, and FGR (gene), Fgr, forming the SrcA subfamily, Lck, HCK, Hck, Tyrosine-protein kinase BLK, Blk, and Lyn (Src family Kinase), Lyn in the SrcB subfamily, and FRK (gene), Frk in its own subfamily. Frk has homologs in invertebrates such as flies and worms, and Src homologs exist in organisms as diverse as unicellular choanoflagellates, but the SrcA and SrcB subfamilies are specific to vertebrates. Src family kinases contain six conserved domains: a N-terminal Myristoylation, myristoylated segment, a SH2 domain, a SH3 domain, a linker region, a tyrosine kinase domain, and C-terminal tail. Src family kinases interact with many cellular cytosolic, nuclear and membrane proteins, modifying these proteins by phosphorylation of tyrosine residues. A number of substrates have been discovered for these enzymes. Deregulation, including constitutive activation or ...
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Reactive Oxygen Species
In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl radical (OH.), and singlet oxygen(1O2). ROS are pervasive because they are readily produced from O2, which is abundant. ROS are important in many ways, both beneficial and otherwise. ROS function as signals, that turn on and off biological functions. They are intermediates in the redox behavior of O2, which is central to fuel cells. ROS are central to the photodegradation of organic pollutants in the atmosphere. Most often however, ROS are discussed in a biological context, ranging from their effects on aging and their role in causing dangerous genetic mutations. Inventory of ROS ROS are not uniformly defined. All sources include superoxide, singlet oxygen, and hydroxyl radical. Hydrogen peroxide is not nearly as reactive as these s ...
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Constitutive Activation
In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a receptor and produce physiological responses, such as a change in the electrical activity of a cell. For example, GABA, an inhibitory neurotransmitter, inhibits electrical activity of neurons by binding to GABA receptors. There are three main ways the action of the receptor can be classified: relay of signal, amplification, or integration. Relaying sends the signal onward, amplification increases the effect of a single ligand, and integration allows the signal to be incorporated into another biochemical pathway. Receptor proteins can be classified by their location. Cell surface receptors, also known as transmembrane receptors, include ligand-gated ion channels, G protein-coupled receptors, and enzyme-linked hormone receptors. Intracellular rece ...
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Intracellular Signaling Pathway
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding (or signal sensing) in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a signaling pathway. When signaling pathways interact with one another they form networks, which allow cellular responses to be coordinated, often by combinatorial signaling events. At the molecular level, such responses include changes in the transcription or translation of genes, and post-translational and conformational changes in proteins, as well as changes in their location. These molecular events are the basic mechanisms controlling cell growth, proliferation, metabolism and many other processes. In multicellular organisms, signal transduction pathways regulat ...
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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 prolife ...
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