Receptor tyrosine kinases (RTK)s are the high affinity cell surface receptors for many polypeptide growth factors, cytokines and hormones. Of the ninety unique tyrosine kinase genes idenitified in the human genome, 58 encode receptor tyrosine kinase proteins.^[1] Receptor tyrosine kinases have been shown to be not only key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer.^[2] In chemistry and biochemistry, a dissociation constant or an ionization constant is a specific type of equilibrium constant used for reversible reactions or processes. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... Growth factor is a protein that acts as a signaling molecule between cells (like cytokines and hormones) that attaches to specific receptors on the surface of a target cell and promotes differentiation and maturation of these cells. ... Cytokines are a group of proteins and peptides that are used in organisms as signaling compounds. ... For other uses, see Hormone (disambiguation). ... For other uses, see Gene (disambiguation). ... A graphical representation of the normal human karyotype. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ...

Receptor tyrosine kinase classes

Approximately 20 different RTK classes have been identified.^[3]

1. RTK class I (EGF receptor family)
2. RTK class II (Insulin receptor family)
3. RTK class III (PDGF receptor family)
4. RTK class IV (FGF receptor family)
5. RTK class V (VEGF receptor family)
6. RTK class VI (HGF receptor family)
7. RTK class VII (Trk receptor family)
8. RTK class IX (AXL receptor family)
9. RTK class X (LTK receptor family)
10. RTK class XI (TIE receptor family)
11. RTK class XII (ROR receptor family)
12. RTK class XIII (DDR receptor family)
13. RTK class XIV (RET receptor family)
14. RTK class XV (KLG receptor family)
15. RTK class XVI (RYK receptor family)
16. RTK class XVII (MuSK receptor family)

The ErbB protein family or epidermal growth factor receptor (EGFR) family is a family of four structurally related receptor tyrosine kinases. ... In molecular biology, the insulin receptor is a transmembrane receptor that is activated by insulin. ... The platelet-derived growth factors PDGF-A and -B have for already more than 30 years been recognized as important factors regulating cell proliferation, cellular differentiation, cell growth, development and many diseases including cancer. ... The fibroblast growth factor receptors are, as their name implies, receptors which bind to members of the fibroblast growth factor family of proteins. ... Receptors for Vascular Endothelial Growth Factor: VEGF. Vascular endothelial growth factor (VEGF) is an important signaling protein involved in both vasculogenesis (the formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). ... c-MET is a pro-oncogene. ... Trk receptors are a family of tyrosine kinases that regulates synaptic strength and plasticity in the mammalian nervous system. ... For the Guns N Roses lead singer, see Axl Rose. ... LTK may refer to the LTK Commune Leukocyte tyrosine kinase in biochemistry, a member of the receptor tyrosine kinase family of cell surface receptors License to Kill Little Kimble railway station, England; National Rail station code LTK. Category: ... Look up ROR in Wiktionary, the free dictionary. ... The RET proto-oncogene encodes a receptor tyrosine kinase for members of the glial cell line-derived neurotrophic factor family of extracellular signalling molecules. ... There are very few or no other articles that link to this one. ... The related to receptor tyrosine kinases (RYKs) are a family of proteins that are a members of the receptor tyrosine kinase family of cell surface receptors. ... // MuSK is required for formation of the Neuromuscular Junction During development, the growing end of motor neuron axons secrete a protein called agrin. ...

Structure

Most RTKs are single subunit receptors but some e.g. the insulin receptor exist as multimeric complexes. Each monomer has a single transmembrane spanning domain composed of 25-38 amino acids, an extracellular N-terminal region and an intracellular C-terminal region. The extracellular N-terminal region is composed of a very large protein domain which binds to extracellular ligands e.g. a particular growth factor or hormone. The intracellular C-terminal region comprises domains responsible for the kinase activity of these receptors. In molecular biology, the insulin receptor is a transmembrane receptor that is activated by insulin. ... In structural biology, a protein subunit or subunit protein is a double protein molecule that assembles (or coassembles) with other protein molecules to form a multimeric or oligomeric protein. ... In chemistry, a monomer (from Greek mono one and meros part) is a small molecule that may become chemically bonded to other monomers to form a polymer. ... A transmembrane protein is a protein that spans the entire biological membrane. ... --RAG 01:54, 16 March 2007 (UTC) The concept of the domain was first proposed in 1973 by Wetlaufer after X-ray crystallographic studies of hen lysozyme (Phillips, 1966), papain (Drenth et al. ... This article is about the class of chemicals. ... In cell biology, molecular biology and related fields, the word extracellular means outside the cell. It is used in contrast to intracellular (inside the cell). ... The N-terminal end refers to the extremity of a protein or polypeptide terminated by an amino acid with a free amine group (NH2). ... In cell biology, molecular biology and related fields, the word intracellular means inside the cell. It is used in contrast to extracellular (outside the cell). ... The C-terminal end refers to the extremity of a protein or polypeptide terminated by an amino acid with a free carboxyl group (COOH). ... --RAG 01:54, 16 March 2007 (UTC) The concept of the domain was first proposed in 1973 by Wetlaufer after X-ray crystallographic studies of hen lysozyme (Phillips, 1966), papain (Drenth et al. ... It has been suggested that this article or section be merged with ligand. ... Growth factor is a protein that acts as a signaling molecule between cells (like cytokines and hormones) that attaches to specific receptors on the surface of a target cell and promotes differentiation and maturation of these cells. ... For other uses, see Hormone (disambiguation). ... In biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific target molecules (substrates); the process is termed phosphorylation. ...

Kinase activity

In biochemistry, a kinase is a type of enzyme that transfers phosphate groups (see below) from high-energy donor molecules, such as ATP (see below) to specific target molecules (substrates); the process is termed phosphorylation. The opposite, an enzyme that removes phosphate groups from targets, is known as a phosphatase. Kinase enzymes that specifically phosphorylate tyrosine amino acids are termed tyrosine kinases. Biochemistry (from Greek: , bios, life and Egyptian kēme, earth[1]) is the study of the chemical processes in living organisms. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... A phosphate, in inorganic chemistry, is a salt of phosphoric acid. ... High energy phosphate can mean one of a couple things: It can mean the phosphate-phosphate bonds formed when compounds such as adenosine diphosphate and adenosine triphosphate are created. ... Adenosine 5-triphosphate (ATP) is a multifunctional nucleotide that is most important as a molecular currency of intracellular energy transfer. ... For other uses, see Substrate. ... A phosphorylated serine residue Phosphorylation is the addition of a phosphate (PO4) group to a protein molecule or a small molecule. ... A phosphatase is an enzyme that dephosphorylates its substrate; i. ... Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ...

Phosphate

ATP

Tyrosine

When a growth factor binds to the extracellular domain of an RTK, its dimerization is triggered with other adjacent RTKs. Dimerization leads to a rapid activation of the proteins cytoplasmic kinase domains, the first substrate for these domains being the receptor itself. The activated receptor as a result then becomes autophosphorylated on multiple specific intracellular tyrosine residues. Dimerization is the formation of a polymer from two similar chemical structures. ... Dimerization is the formation of a polymer from two similar chemical structures. ... Tyrosine (from the Greek tyros, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese[1][2]), 4-hydroxyphenylalanine, or 2-amino-3(4-hydroxyphenyl)-propanoic acid, is one of the 20 amino acids that are used by cells... A residue, broadly, is anything left behind by a reaction or event. ...

Signal transduction

The phosphorylation of specific tyrosine residues within the activated receptor creates binding sites for Src homology 2 (SH2) and phosphotyrosine binding (PTB) domain containing proteins.^[4] Specific proteins containing these domains include Src and phospholipase Cγ, the phosphorylation and activation of these two proteins on receptor binding leading to the initiation of signal transduction pathways. Other proteins that interact with the activated receptor act as adaptor proteins and have no intrinsic enzymatic activity of their own. These adaptor proteins link RTK activation to downstream signal transduction pathways, such as the MAP kinase signalling cascade.^[2] Tyrosine (from the Greek tyros, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese[1][2]), 4-hydroxyphenylalanine, or 2-amino-3(4-hydroxyphenyl)-propanoic acid, is one of the 20 amino acids that are used by cells... A residue, broadly, is anything left behind by a reaction or event. ... Ribbon diagram of the SH2 domain of human P56-Lck tyrosine kinase (PDB accession code 1LKK, chain A), colored from blue (N-terminus) to red (C-terminus). ... Tyrosine (from the Greek tyros, meaning cheese, as it was first discovered in cheese), 4-hydroxyphenylalanine, or 2-amino-3(4-hydroxyphenyl)-propanoic acid, is one of the 20 amino acids that are used by cells to synthesize proteins. ... Src is a family of proto-oncogenes that may lead to cancer. ... Phospholipase C is a key enzyme in phosphatidylinositol (PIP2) metabolism and lipid signaling pathways. ... In biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another, most often involving ordered sequences of biochemical reactions inside the cell, that are carried out by enzymes and linked through second messengers resulting in what is thought of as... An adaptor protein is a protein which is accessory to main proteins in signal transduction. ... In biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another, most often involving ordered sequences of biochemical reactions inside the cell, that are carried out by enzymes and linked through second messengers resulting in what is thought of as... In cell biology, mitogen-activated protein kinases (MAPKs) (EC 2. ...

Families

Fibroblast growth factor receptor (FGFR) family

For more details on this topic, see fibroblast growth factor receptor.

The fibroblast growth factors are the largest family of growth factor ligands comprising of 23 members.^[5] The natural alternate splicing of four fibroblast growth factor receptor (FRFR) genes results in the production of over 48 different isoforms of FGFR.^[6] These isoforms vary in their ligand binding properties and kinase domains, however all share a common extracellular region composed of three immunoglobulin (Ig) like domains (D1-D3), and thus belong to the immunoglobulin superfamily.^[7] Interactions with FGFs occur via FGFR domains D2 and D3. Each receptor can be activated by several FGFs. In many cases the FGFs themselves can also activate more than one receptor, this is not the case with FGF-7 however which can only activate FGFR2b.^[6] A gene for a fifth FGFR protein, FGFR5, has also been identified. In contrast to FGFRs 1-4 it lacks a cytoplasmic tyrosine kinase domain and one isoform, FGFR5γ, only contains the extracellular domains D1 and D2.^[8] So far, four distinct membrane FGFR have been identified in vertebrates and all of them belong to the tyrosine kinase superfamily (FGFR1 to FGFR4). ... Fibroblast growth factors, or FGFs, are a family of growth factors involved in wound healing and embryonic development. ... Genetic engineering, genetic modification (GM), and gene splicing (once in widespread use but now deprecated) are terms for the process of manipulating genes in an organism, usually outside of the organisms normal reproductive process. ... In biology, a protein isoform is a version of a protein with some small differences, usually a splice variant or the product of some posttranslational modification. ... Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Cell Adhesion Molecules (CAMs) are proteins located on the cell surface involved with the binding with other cells or with the extracellular matrix (ECM) in the process called cell adhesion. ...

Vascular endothelial growth factor receptor (VEGFR) family

For more details on this topic, see VEGF.

Vascular endothelial growth factor (VEGF) is one of the main inducers of endothelial cell proliferation and permeability of blood vessels. Two RTKs bind to VEGF at the cell surface, VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1).^[9] Vascular endothelial growth factor or VEGF is an important signal protein involved in angiogenesis. ... Vascular endothelial growth factor (VEGF) is an important signaling protein involved in both vasculogenesis (the de novo formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ... The blood vessels are part of the circulatory system and function to transport blood throughout the body. ... Receptors for Vascular Endothelial Growth Factor: VEGF. Vascular endothelial growth factor (VEGF) is an important signaling protein involved in both vasculogenesis (the formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Kinase insert domain receptor (a type III receptor tyrosine kinase), also known as KDR, is a human gene. ...

The VEGF receptors have an extracellular portion consisting of seven Ig-like domains so, like FGFRs, belong to the immunoglobulin superfamily. They also possess a single transmembrane spanning region and an intracellular portion containing a split tyrosine-kinase domain. VEGF-A binds to VEGFR-1 (Flt-1) and VEGFR-2 (KDR/Flk-1). VEGFR-2 appears to mediate almost all of the known cellular responses to VEGF. The function of VEGFR-1 is less well defined, although it is thought to modulate VEGFR-2 signaling. Another function of VEGFR-1 may be to act as a dummy/decoy receptor, sequestering VEGF from VEGFR-2 binding (this appears to be particularly important during vasculogenesis in the embryo). A third receptor has been discovered (VEGFR-3), however, VEGF-A is not a ligand for this receptor. VEGFR-3 mediates lymphangiogenesis in response to VEGF-C and VEGF-D. Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ... Receptors for Vascular Endothelial Growth Factor: VEGF. Vascular endothelial growth factor (VEGF) is an important signaling protein involved in both vasculogenesis (the formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Kinase insert domain receptor (a type III receptor tyrosine kinase), also known as KDR, is a human gene. ... Lymphangiogesis is the formation of lymphatic vessels from a pre-existing lymphatic vessels, in a method believed to be similar to blood vessel development or angiogenesis. ...

RET receptor family

For more details on this topic, see RET proto-oncogene.

The natural alternate splicing of the RET gene results in the production of 3 different isoforms of the protein RET. RET51, RET43 and RET9 contain 51, 43 and 9 amino acids in their C-terminal tail respectively.^[10] The biological roles of isoforms RET51 and RET9 are the most well studied in-vivo as these are the most common isoforms in which RET occurs. The RET proto-oncogene encodes a receptor tyrosine kinase for members of the glial cell line-derived neurotrophic factor family of extracellular signalling molecules. ... Genetic engineering, genetic modification (GM), and gene splicing (once in widespread use but now deprecated) are terms for the process of manipulating genes in an organism, usually outside of the organisms normal reproductive process. ... For other uses, see Gene (disambiguation). ... In biology, a protein isoform is a version of a protein with some small differences, usually a splice variant or the product of some posttranslational modification. ... This article is about the class of chemicals. ... The C-terminal end refers to the extremity of a protein or polypeptide terminated by an amino acid with a free carboxyl group (COOH). ... In biology, a protein isoform is a version of a protein with some small differences, usually a splice variant or the product of some posttranslational modification. ... In vivo (Latin for (with)in the living). ...

RET is the receptor for members of the glial cell line-derived neurotrophic factor (GDNF) family of extracellular signalling molecules or ligands (GFLs).^[11] Glial cell line-Derived Neurotrophic Factor (GDNF) is a small protein that potently promotes the survival of many types of neurons. ... In biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another, most often involving ordered sequences of biochemical reactions inside the cell, that are carried out by enzymes and linked through second messengers resulting in what is thought of as... It has been suggested that this article or section be merged with ligand. ...

In order to activate RET GFLs first need to form a complex with a glycosylphosphatidylinositol (GPI)-anchored co-receptor. The co-receptors themselves are classified as members of the GDNF receptor-α (GFRα) protein family. Different members of the GFRα family (GFRα1-GFRα4) exhibit a specific binding activity for a specific GFLs.^[12] Upon GFL-GFRα complex formation, the complex then brings together two molecules of RET, triggering trans-autophosphorylation of specific tyrosine residues within the tyrosine kinase domain of each RET molecule. Phosphorylation of these tyrosines then initiates intracellular signal transduction processes.^[13] A protein complex is a group of two or more associated proteins formed by protein-protein interaction that is stable over time. ... It is a protein which can be found anchored in plasma membranes. ... This page is a candidate to be copied to Wiktionary. ... A protein kinase is an enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation). ... Tyrosine (from the Greek tyros, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese[1][2]), 4-hydroxyphenylalanine, or 2-amino-3(4-hydroxyphenyl)-propanoic acid, is one of the 20 amino acids that are used by cells... Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ... A phosphorylated serine residue Phosphorylation is the addition of a phosphate (PO4) group to a protein molecule or a small molecule. ... Tyrosine (from the Greek tyros, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese[1][2]), 4-hydroxyphenylalanine, or 2-amino-3(4-hydroxyphenyl)-propanoic acid, is one of the 20 amino acids that are used by cells... In biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another, most often involving ordered sequences of biochemical reactions inside the cell, that are carried out by enzymes and linked through second messengers resulting in what is thought of as...

References

Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era in the 21st century. ... is the 95th day of the year (96th in leap years) in the Gregorian calendar. ...

See also

• Tyrosine kinase
• Insulin receptor
• Enzyme-linked receptor

Tyrosine kinases are a subclass of protein kinase, see there for the principles of protein phosphorylation A tyrosine kinase (EC 2. ... In molecular biology, the insulin receptor is a transmembrane receptor that is activated by insulin. ... An enzyme-linked receptor is a transmembrane receptor, where the binding of an extracellular ligand causes enzymatic activity on the intracellular side. ...

External links

• MeSH Tyrosine+Kinase+Receptors
• EC 2.7.10.1