Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages ; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their function lead to a range of developmental defects. These growth factors typically act as systemic or locally circulating molecules of extracellular origin that activate cell surface receptors. A defining property of FGFs is that they bind to heparin and to heparan sulfate . Thus, some are sequestered in the extracellular matrix of tissues that contains heparan sulfate proteoglycans and are released locally upon injury or tissue remodeling.
29-640: FGF may refer to: Fibroblast growth factor Galician Football Federation (Spanish: Federación Galega de Fútbol ), in Spain Guinean Football Federation (French: Fédération Guinéenne de Football ) Federação Gaúcha de Futebol , the Football Federation of Rio Grande do Sul, Brazil Federação Goiana de Futebol , the Football Federation of Goiás, Brazil Fédération générale des fonctionnaires ,
58-442: A stimulus (ex. drugs) applied to a subject (ex. animals, tissues, plants). The corresponding response (ex. death) of the subject is thereby triggered and measured. The first use of a bioassay dates back to the late 19th century, when the foundation of bioassays was laid down by German physician Paul Ehrlich. He introduced the concept of standardization by the reactions of living matter. His bioassay on diphtheria antitoxin
87-747: A common measure of acute toxicity, describes the dose at which a substance is lethal to 50% of tested animals. The potency of a drug may be measured using a bioassay. Environmental bioassays are generally a broad-range survey of toxicity . A toxicity identification evaluation is conducted to determine what the relevant toxicants are. Although bioassays are beneficial in determining the biological activity within an organism, they can often be time-consuming and laborious. Organism-specific factors may result in data that are not applicable to others in that species. For these reasons, other biological techniques are often employed, including radioimmunoassays . See bioindicator . Water pollution control requirements in
116-538: A high degree of sequence homology among their amino acid chains, but were determined to be distinct proteins. Not long after FGF1 and FGF2 were isolated, another group of investigators isolated a pair of heparin -binding growth factors that they named HBGF-1 and HBGF-2, while a third group isolated a pair of growth factors that caused proliferation of cells in a bioassay containing blood vessel endothelium cells, which they called ECGF1 and ECGF2. These independently discovered proteins were eventually demonstrated to be
145-568: A single-span trans-membrane domain and an intracellular split tyrosine kinase domain. FGFs interact with the D2 and D3 domains, with the D3 interactions primarily responsible for ligand-binding specificity (see below). Heparan sulfate binding is mediated through the D3 domain. A short stretch of acidic amino acids located between the D1 and D2 domains has auto-inhibitory functions. This 'acid box' motif interacts with
174-490: A substance by its effect on living animals or plants ( in vivo ), or on living cells or tissues ( in vitro ). A bioassay can be either quantal or quantitative, direct or indirect. If the measured response is binary, the assay is quantal ; if not, it is quantitative . A bioassay may be used to detect biological hazards or to give an assessment of the quality of a mixture. A bioassay is often used to monitor water quality as well as wastewater discharges and its impact on
203-611: A trade union for French civil servants Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title FGF . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=FGF&oldid=1145113965 " Category : Disambiguation pages Hidden categories: Articles containing Galician-language text Articles containing French-language text Articles containing Portuguese-language text Short description
232-468: Is added to one plate. If the plate with the suspected mutagen grows more visible colonies, it is probably mutagenic: a mutagen might cause the strain of bacterium to regain the ability to make its own histidine. Most other forms of toxicology testing are also bioassays. Animals or cell cultures may be put under a number of levels of a suspected toxin to ascertain whether the substance causes harmful changes and at what level it does so. The LD 50 value,
261-617: Is classified as paracrine signalling , most commonly through the JAK-STAT signalling pathway or the receptor tyrosine kinase (RTK) pathway. Members of the FGF19 subfamily ( FGF15 , FGF19 , FGF21 , and FGF23 ) bind less tightly to heparan sulfates, and so can act in an endocrine fashion on far-away tissues, such as intestine, liver, kidney, adipose, and bone. For example: The crystal structures of FGF1 have been solved and found to be related to interleukin 1-beta . Both families have
290-421: Is critical during normal development of both vertebrates and invertebrates and any irregularities in their function leads to a range of developmental defects. FGFs secreted by hypoblasts during avian gastrulation play a role in stimulating a Wnt signaling pathway that is involved in the differential movement of Koller's sickle cells during formation of the primitive streak . Left, angiography of
319-504: Is different from Wikidata All article disambiguation pages All disambiguation pages Fibroblast growth factor In humans, 23 members of the FGF family have been identified, all of which are structurally related signaling molecules : The mammalian fibroblast growth factor receptor family has 4 members, FGFR1 , FGFR2 , FGFR3 , and FGFR4 . The FGFRs consist of three extracellular immunoglobulin-type domains (D1-D3),
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#1732779509098348-457: Is the promotion of endothelial cell proliferation and the physical organization of endothelial cells into tube-like structures. They thus promote angiogenesis , the growth of new blood vessels from the pre-existing vasculature . FGF1 and FGF2 are more potent angiogenic factors than vascular endothelial growth factor (VEGF) or platelet-derived growth factor (PDGF). FGF1 has been shown in clinical experimental studies to induce angiogenesis in
377-443: The hippocampus e.g. depends greatly on FGF2. In addition, FGF1 and FGF2 seem to be involved in the regulation of synaptic plasticity and processes attributed to learning and memory, at least in the hippocampus. The 15 exparacrine FGFs are secreted proteins that bind heparan sulfate and can, therefore, be bound to the extracellular matrix of tissues that contain heparan sulfate proteoglycans . This local action of FGF proteins
406-399: The 'universal ligand' as it is capable of activating all 7 different FGFRs. In contrast, FGF7 (keratinocyte growth factor, KGF) binds only to FGFR2b (KGFR). The signalling complex at the cell surface is believed to be a ternary complex formed between two identical FGF ligands, two identical FGFR subunits, and either one or two heparan sulfate chains. A mitogenic growth factor activity
435-413: The FGF signalling system underlies a range of diseases associated with the increased FGF expression. Inhibitors of FGF signalling have shown clinical efficacy. Some FGF ligands (particularly FGF2) have been demonstrated to enhance tissue repair (e.g. skin burns, grafts, and ulcers) in a range of clinical settings. Bioassay A bioassay is an analytical method to determine the potency or effect of
464-462: The United States require some industrial dischargers and municipal sewage treatment plants to conduct bioassays. These procedures, called whole effluent toxicity tests, include acute toxicity tests as well as chronic test methods. The methods involve exposing living aquatic organisms to samples of wastewater for a specific length of time. Another example is the bioassay ECOTOX, which uses
493-524: The biochemistry and pharmacology concept of how a variety of molecules can bind to and elicit a response from single receptor. In the case of FGF, four receptor subtypes can be activated by more than twenty different FGF ligands . Thus the functions of FGFs in developmental processes include mesoderm induction, anterior-posterior patterning, limb development , neural induction and neural development , and in mature tissues/systems angiogenesis , keratinocyte organization, and wound healing processes. FGF
522-406: The canary died due to a build-up of methane, the miners would leave the area as quickly as possible. Many early examples of bioassays used animals to test the carcinogenicity of chemicals. In 1915, Yamaigiwa Katsusaburo and Koichi Ichikawa tested the carcinogenicity of coal tar using the inner surface of rabbit's ears. From the 1940s to the 1960s, animal bioassays were primarily used to test
551-456: The heart. As well as stimulating blood vessel growth, FGFs are important players in wound healing. FGF1 and FGF2 stimulate angiogenesis and the proliferation of fibroblasts that give rise to granulation tissue , which fills up a wound space/cavity early in the wound-healing process. FGF7 and FGF10 (also known as keratinocyte growth factors KGF and KGF2, respectively) stimulate the repair of injured skin and mucosal tissues by stimulating
580-476: The heparan sulfate binding site to prevent receptor activation in the absence of FGFs. Alternate mRNA splicing gives rise to 'b' and 'c' variants of FGFRs 1, 2 and 3. Through this mechanism, seven different signalling FGFR sub-types can be expressed at the cell surface. Each FGFR binds to a specific subset of the FGFs. Similarly, most FGFs can bind to several different FGFR subtypes. FGF1 is sometimes referred to as
609-571: The newly formed vascular network in the region of the front wall of the left ventricle. Right, analysis quantifying the angiogenic effect. While many FGFs can be secreted by cells to act on distant targets, some FGF act locally within a tissue, and even within a cell. Human FGF2 occurs in low molecular weight (LMW) and high molecular weight (HMW) isoforms . LMW FGF2 is primarily cytoplasmic and functions in an autocrine manner, whereas HMW FGF2s are nuclear and exert activities through an intracrine mechanism. One important function of FGF1 and FGF2
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#1732779509098638-467: The proliferation, migration and differentiation of epithelial cells , and they have direct chemotactic effects on tissue remodelling. During the development of the central nervous system , FGFs play important roles in neural stem cell proliferation, neurogenesis , axon growth, and differentiation. FGF signaling is important in promoting surface area growth of the developing cerebral cortex by reducing neuronal differentiation and hence permitting
667-458: The same beta trefoil fold consisting of 12-stranded beta-sheet structure , with the beta-sheets are arranged in 3 similar lobes around a central axis, 6 strands forming an anti-parallel beta-barrel . In general, the beta-sheets are well-preserved and the crystal structures superimpose in these areas. The intervening loops are less well-conserved - the loop between beta-strands 6 and 7 is slightly longer in interleukin-1 beta. Dysregulation of
696-579: The same sets of molecules, namely FGF1, HBGF-1 and ECGF-1 were all the same acidic fibroblast growth factor described by Gospodarowicz, et al., while FGF2, HBGF-2, and ECGF-2 were all the same basic fibroblast growth factor. FGFs are multifunctional proteins with a wide variety of effects; they are most commonly mitogens but also have regulatory, morphological, and endocrine effects. They have been alternately referred to as " pluripotent " growth factors and as "promiscuous" growth factors due to their multiple actions on multiple cell types. Promiscuous refers to
725-490: The self-renewal of cortical progenitor cells, known as radial glial cells , and FGF2 has been used to induce artificial gyrification of the mouse brain . Another FGF family member, FGF8 , regulates the size and positioning of the functional areas of the cerebral cortex ( Brodmann areas ). FGFs are also important for maintenance of the adult brain. Thus, FGFs are major determinants of neuronal survival both during development and during adulthood. Adult neurogenesis within
754-442: The surroundings. It is also used to assess the environmental impact and safety of new technologies and facilities. Bioassays are essential in pharmaceutical, medical and agricultural sciences for development and launching of new drugs, vitamins, etc. A bioassay is a biochemical test to estimate the potency of a sample compound. Usually this potency can only be measured relative to a standard compound. A typical bioassay involves
783-606: The toxicity and safety of drugs, food additives, and pesticides. Beginning in the late 1960s and 1970s, reliance on bioassays increased as public concern for occupational and environmental hazards increased. Bioassay can be classified by how it is applied and how the response is recorded. One classical bioassay is the Ames test . A strain of Salmonella that requires histidine to grow is put on two plates with growth medium containing minimal amounts of histidine and some rat liver extract (to mimick liver metabolism). A suspected mutagen
812-570: Was found in pituitary extracts by Armelin in 1973 and further work by Gospodarowicz as reported in 1974 described a more defined isolation of proteins from cow brain extract which, when tested in a bioassay that caused fibroblasts to proliferate , led these investigators to apply the name "fibroblast growth factor." In 1975, they further fractionated the extract using acidic and basic pH and isolated two slightly different forms that were named "acidic fibroblast growth factor" (FGF1) and "basic fibroblast growth factor" (FGF2). These proteins had
841-419: Was the first bioassay to receive recognition. His use of bioassay was able to discover that administration of gradually increasing dose of diphtheria in animals stimulated production of antiserum. One well known example of a bioassay is the "canary in the coal mine" experiment. To provide advance warning of dangerous levels of methane in the air, miners would take methane-sensitive canaries into coal mines. If
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