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Receptor Tyrosine Kinases
Receptor tyrosine kinases (RTKs) are the high- affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Mutations in receptor tyrosine kinases lead to activation of a series of signalling cascades which have numerous effects on protein expression. Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non-receptor tyrosine kinases which do not possess transmembrane domains. History The first RTKs to be discovered were EGF and NGF in the 1960s, but the classification of receptor tyrosine kinases was not ...
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Dissociation Constant
In chemistry, biochemistry, and pharmacology, a dissociation constant (K_D) is a specific type of equilibrium constant that measures the propensity of a larger object to separate (dissociate) reversibly into smaller components, as when a complex falls apart into its component molecules, or when a salt splits up into its component ions. The dissociation constant is the inverse of the association constant. In the special case of salts, the dissociation constant can also be called an ionization constant. For a general reaction: : A_\mathit B_\mathit \mathit A + \mathit B in which a complex \ce_x \ce_y breaks down into ''x'' A subunits and ''y'' B subunits, the dissociation constant is defined as : K_D = \frac where and ''x'' B''y''are the equilibrium concentrations of A, B, and the complex A''x'' B''y'', respectively. One reason for the popularity of the dissociation constant in biochemistry and pharmacology is that in the frequently enc ...
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Trk Receptor
Trk receptors are a family of tyrosine kinases that regulates synaptic strength and plasticity in the mammalian nervous system. Trk receptors affect neuronal survival and differentiation through several signaling cascades. However, the activation of these receptors also has significant effects on functional properties of neurons. The common ligands of trk receptors are neurotrophins, a family of growth factors critical to the functioning of the nervous system. The binding of these molecules is highly specific. Each type of neurotrophin has different binding affinity toward its corresponding Trk receptor. The activation of Trk receptors by neurotrophin binding may lead to activation of signal cascades resulting in promoting survival and other functional regulation of cells. Origin of the name ''trk'' The abbreviation ''trk'' (often pronounced 'track') stands for tropomyosin receptor kinase or ''tyrosine'' receptor kinase (and not "''tyrosine'' kinase receptor" nor "tropomyo ...
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Insulin Receptor
The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of receptor tyrosine kinase. Metabolically, the insulin receptor plays a key role in the regulation of glucose homeostasis, a functional process that under degenerate conditions may result in a range of clinical manifestations including diabetes and cancer. Insulin signalling controls access to blood glucose in body cells. When insulin falls, especially in those with high insulin sensitivity, body cells begin only to have access to lipids that do not require transport across the membrane. So, in this way, insulin is the key regulator of fat metabolism as well. Biochemically, the insulin receptor is encoded by a single gene , from which alternate splicing during transcription results in either IR-A or IR-B isoforms. Downstream post-translational events of either isoform result in the formation of a proteolytically cleaved α and β subunit, which upo ...
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Protein Subunit
In structural biology, a protein subunit is a polypeptide chain or single protein molecule that assembles (or "''coassembles''") with others to form a protein complex. Large assemblies of proteins such as viruses often use a small number of types of protein subunits as building blocks. A subunit is often named with a Greek or Roman letter, and the numbers of this type of subunit in a protein is indicated by a subscript. For example, ATP synthase has a type of subunit called α. Three of these are present in the ATP synthase molecule, leading to the designation α3. Larger groups of subunits can also be specified, like α3β3-hexamer and c-ring. Naturally-occurring proteins that have a relatively small number of subunits are referred to as oligomeric.Quote: ''Oligomer molecule: A molecule of intermediate relative molecular mass, the structure of which essentially comprises a small plurality of units derived, actually or conceptually, from molecules of lower relative molecular ...
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MuSK Protein
MuSK (for Muscle-Specific Kinase) is a receptor tyrosine kinase required for the formation and maintenance of the neuromuscular junction. It is activated by a nerve-derived proteoglycan called agrin, which is similarly also required for neuromuscular junction formation. MuSK signaling Upon activation by its ligand agrin, MuSK signals via the proteins called casein kinase 2 (CK2), Dok-7 and rapsyn, to induce "clustering" of acetylcholine receptors ( AChR). Both CK2 and Dok-7 are required for MuSK-induced formation of the neuromuscular junction, since mice lacking Dok-7 failed to form AChR clusters or neuromuscular synapses, and since downregulation of CK2 also impedes recruitment of AChR to the primary MuSK scaffold. In addition to the proteins mentioned, other proteins are then gathered, to form the endplate to the neuromuscular junction. The nerve terminates onto the endplate, forming the neuromuscular junction - a structure required to transmit nerve impulses to the muscle, an ...
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Receptor Tyrosine Kinase-like Orphan Receptor
In the field of molecular biology, receptor tyrosine kinase-like orphan receptors (RORs) are a family of tyrosine kinase receptors that are important in regulating skeletal and neuronal development, cell migration and cell polarity. ROR proteins ( ROR1 and ROR2 Tyrosine-protein kinase transmembrane receptor ROR2, also known as neurotrophic tyrosine kinase, receptor-related 2, is a protein that in humans is encoded by the ''ROR2'' gene located on position 9 of the long arm of chromosome 9. This protein ... in humans) can modulate Wnt signaling by sequestering Wnt ligands. References {{Portal bar, Biology, border=no Tyrosine kinase receptors ...
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Leukocyte Receptor Tyrosine Kinase
Leukocyte receptor tyrosine kinase is an enzyme that in humans is encoded by the ''LTK'' gene. Function The protein encoded by this gene is a member of the ALK/LTK receptor family of receptor tyrosine kinases (RTKs) whose ligand is unknown. Closely related to the insulin receptor family of RTKs. Tyrosine-specific phosphorylation of proteins is a key to the control of diverse pathways leading to cell growth and differentiation. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. Interactions LTK has been shown to interact with IRS-1, Shc, and PIK3R1 Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the ''PIK3R1'' gene. Function Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The e .... References Further reading * * * * * * * * * * * * Tyrosine kinase receptors {{gene-15-st ...
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ROS1
Proto-oncogene tyrosine-protein kinase ROS is an enzyme that in humans is encoded by the ''ROS1'' gene. Function This proto-oncogene, highly expressed in a variety of tumor cell lines, belongs to the sevenless subfamily of tyrosine kinase insulin receptor genes. The protein encoded by this gene is a type I integral membrane protein with tyrosine kinase activity. The protein may function as a growth or differentiation factor receptor. Role in cancer ''ROS1'' is a receptor tyrosine kinase (encoded by the gene ''ROS1'') with structural similarity to the anaplastic lymphoma kinase (ALK) protein; it is encoded by the ''c-ros'' oncogene and was first identified in 1986. The exact role of the ''ROS1'' protein in normal development, as well as its normal physiologic ligand, have not been defined. Nonetheless, as gene rearrangement events involving ''ROS1'' have been described in lung and other cancers, and since such tumors have been found to be remarkably responsive to small m ...
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RET Proto-oncogene
The ''RET'' proto-oncogene encodes a receptor tyrosine kinase for members of the glial cell line-derived neurotrophic factor (GDNF) family of extracellular signalling molecules. ''RET'' loss of function mutations are associated with the development of Hirschsprung's disease, while gain of function mutations are associated with the development of various types of human cancer, including medullary thyroid carcinoma, multiple endocrine neoplasias type 2A and 2B, pheochromocytoma and parathyroid hyperplasia. Structure ''RET'' is an abbreviation for "rearranged during transfection", as the DNA sequence of this gene was originally found to be rearranged within a 3T3 fibroblast cell line following its transfection with DNA taken from human lymphoma cells. The human gene ''RET'' is localized to chromosome 10 (10q11.2) and contains 21 exons. The natural alternative splicing of the ''RET'' gene results in the production of 3 different isoforms of the protein RET. RET51, RET4 ...
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DDR1
Discoidin domain receptor family, member 1, also known as DDR1 or CD167a (cluster of differentiation 167a), is a human gene. Function Receptor tyrosine kinases (RTKs) play a key role in the communication of cells with their microenvironment. These molecules are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene is a RTK that is widely expressed in normal and transformed epithelial cells and is activated by various types of collagen. This protein belongs to a subfamily of tyrosine kinase receptors with a homology region to the ''Dictyostelium discoideum'' protein discoidin I in their extracellular domain. Its autophosphorylation is achieved by all collagens so far tested (type I to type VI). A closely related family member is the DDR2 protein. In situ studies and Northern-blot analysis showed that expression of this encoded protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tr ...
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Related To Receptor Tyrosine Kinase
The related to receptor tyrosine kinase (RYK) gene encodes the protein Ryk. The protein encoded by this gene is an atypical member of the family of growth factor receptor protein tyrosine kinases, differing from other members at a number of conserved residues in the activation and nucleotide binding domains. This gene product belongs to a subfamily whose members do not appear to be regulated by phosphorylation in the activation segment. It has been suggested that mediation of biological activity by recruitment of a signaling-competent auxiliary protein may occur through an as yet uncharacterized mechanism. Two alternative splice variants have been identified, encoding distinct isoforms. History The gene encoding mouse RYK was first identified in 1992. Subsequently, cDNA encoding the RYK protein have been isolated from the following species. * rat *chicken *Human *Zebrafish *''Caenorhabditis elegans'' *''Drosophila'' Structure In common with other receptor tyrosine kinase famil ...
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Angiopoietin Receptor
The angiopoietin receptors are receptors that bind angiopoietin. TIE-1 and TIE-2 comprise the cell-surface receptors that bind and are activated by the angiopoietins, (Ang1, Ang2, Ang3, Ang4). The angiopoietins are protein growth factors required for the formation of blood vessels (angiogenesis). Angiopoietins The angiopoietins are protein growth factors that regulate angiogenesis, the formation of blood vessels. In humans, three angiopoietins have been identified: Ang1, Ang2, and Ang4 (Ang 3 is the mouse ortholog of human Ang4). Ang1 and Ang4 function as agonistic or activating ligands for Tie2, whereas Ang2 and Ang3 behave as competitive antagonists. They function by binding their physiologic receptors, Tie-1 and Tie-2. These are receptor tyrosine kinases, so named because they mediate cell signals by inducing the phosphorylation of key tyrosines, thus initiating cell signalling In biology, cell signaling (cell signalling in British English) or cell communication is ...
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