Information about Fibroblast Growth Factors
Fibroblast growth factors, or FGFs, are a family of growth factors involved in wound healing and embryonic development. The FGFs are heparin-binding proteins and interactions with cell-surface associated heparan sulfate proteoglycans have been shown to be essential for FGF signal transduction.
Alternate mRNA splicing gives rise to multiple mRNA splice variants, of which the FGFR2IIIb splice variant encode isoform 2, the canonical FGF-10 receptor. 13 protein receptor isoforms are derived from the FGFR2 gene, e.ge., and the active sites differ significantly in their ligand-binding profiles.
The signaling 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 (dermatan and/or chondroitin) sulfate chains.
They then 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 a high degree of amino acid identity but were determined to be distinct mitogens. Human FGF2 occurs in low molecular weight (LMW) and high molecular weight (HMW) isoforms.[4] LMW FGF2 is primarily cytoplasmic and functions in an autocrine manner, whereas HMW FGF-2s are nuclear and exert activities through an intracrine mechanism.
Not long after FGF1 and FGF2 were isolated, another group isolated a pair of heparin-binding growth factors which they named HBGF-1 and HBGF-2, whilst 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 ECGF-1 and ECGF-2. These proteins were found to be identical to the acidic and basic FGFs described by Gospodarowicz and coworkers.
It has also been demonstrated that fibroblast growth factors are associated with many developmental processes including mesoderm induction, antero-posterior patterning, neural induction, angiogenesis, axon extension and limb formation.[5]
They are crucial for the normal development of both vertebrates and invertebrates and any irregularities in their function leads to a range of developmental defects.[6] [7] [8] [9]
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Families
In humans, 20 members of the FGF family have been identified all of which are structurally related signaling molecules:[1]- Members FGF1 through FGF10 all bind fibroblast growth factor receptors (FGFRs). FGF1 is also known as "Acidic", and FGF2 is also known as basic fibroblast growth factor.
- Members FGF11, FGF12, FGF13, and FGF14, also known as FGF homologous factors 1-4 (FHF1-FHF4), have been shown to have distinct functional differences compared to the FGFs. Although these factors possess remarkably similar sequence homology, they do not bind FGFRs and are involved in intracellular processes unrelated to the FGFs.[2]
- Members FGF16 through FGF23 are newer and not as well characterized. FGF15 is the mouse ortholog of human FGF19.
Receptors
The fibroblast growth factor receptor family consists of 4 members, FGFR1, FGFR2, FGFR3, and FGFR4.Alternate mRNA splicing gives rise to multiple mRNA splice variants, of which the FGFR2IIIb splice variant encode isoform 2, the canonical FGF-10 receptor. 13 protein receptor isoforms are derived from the FGFR2 gene, e.ge., and the active sites differ significantly in their ligand-binding profiles.
The signaling 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 (dermatan and/or chondroitin) sulfate chains.
History
Fibroblast growth factor was found in a cow brain extract by Gospodarowicz and colleagues and tested in a bioassay which caused fibroblasts to proliferate (first published report in 1974).[3]They then 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 a high degree of amino acid identity but were determined to be distinct mitogens. Human FGF2 occurs in low molecular weight (LMW) and high molecular weight (HMW) isoforms.[4] LMW FGF2 is primarily cytoplasmic and functions in an autocrine manner, whereas HMW FGF-2s are nuclear and exert activities through an intracrine mechanism.
Not long after FGF1 and FGF2 were isolated, another group isolated a pair of heparin-binding growth factors which they named HBGF-1 and HBGF-2, whilst 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 ECGF-1 and ECGF-2. These proteins were found to be identical to the acidic and basic FGFs described by Gospodarowicz and coworkers.
Function
One of the most important functions of bFGF (FGF2) is the promotion of endothelial cell proliferation and the physical organization of endothelial cells into tube-like structures. It thus promotes angiogenesis, the growth of new blood vessels from the pre-existing vasculature. bFGF is a more potent angiogenic factor than VEGF (vascular endothelial growth factor) or PDGF (platelet-derived growth factor). As well as stimulating blood vessel growth, bFGF is an important player in wound healing. It stimulates the proliferation of fibroblasts that give rise to granulation tissue, which fills up a wound space/cavity early in the wound healing process.It has also been demonstrated that fibroblast growth factors are associated with many developmental processes including mesoderm induction, antero-posterior patterning, neural induction, angiogenesis, axon extension and limb formation.[5]
They are crucial for the normal development of both vertebrates and invertebrates and any irregularities in their function leads to a range of developmental defects.[6] [7] [8] [9]
See also
- granulocyte-colony stimulating factor (G-CSF)
- granulocyte-macrophage colony stimulating factor (GM-CSF)
- nerve growth factor (NGF)
- neurotrophins
- erythropoietin (EPO)
- thrombopoietin (TPO)
- myostatin (GDF-8)
- Growth Differentiation factor-9 (GDF9)
References
1. ^ Finklestein S.P. and Plomaritoglou A. (2001). "Growth factors", in Miller L.P. and Hayes R.L., eds. Co-edited by Newcomb J.K.: Head Trauma: Basic, Preclinical, and Clinical Directions. John Wiley and Sons, Inc. New York, 165-187. ISBN 0471360155.
2. ^ Olsen SK, Garbi M. et al (2003). "Fibroblast growth factor (FGF) homologous factors share structural but not functional homology with FGFs". J. Biol. Chem. 278 (36): 34226-34236. PMID 12815063.
3. ^ Gospodarowicz D (1974). "Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth". Nature 249 (453): 123-7. PMID 4364816.
4. ^ Arese M, Chen Y. et al (1999). "Nuclear activities of basic fibroblast growth factor: potentiation of low-serum growth mediated by natural or chimeric nuclear localization signals.". Mol. Biol. Cell 10 (5): 1429-1444. PMID 10233154.
5. ^ Böttcher RT, Niehrs C. (2005). "Fibroblast growth factor signaling during early vertebrate development". Endocr. Rev. 26 (1): 63-77. PMID 15689573.
6. ^ Amaya E, Musci T.J. and Kirschner M.W. (1991). "Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos". Cell 66 (2): 257-270. PMID 1649700.
7. ^ Borland C.Z., Schutzman J.L. and Stern M.J. (2001). "Fibroblast growth factor signaling in Caenorhabditis elegans". Bioessays 23 (12): 1120-1130. PMID 11746231.
8. ^ Coumoul X. and Deng C.X. (2003). "Roles of FGF receptors in mammalian development and congenital diseases". Birth Defects Res C Embryo Today 69 (4): 286-304. PMID 14745970.
9. ^ Sutherland D, Samakovlis C . and Krasnow M.A. (1996). "Branchless encodes a Drosophila FGF homolog that controls tracheal cell migration and the pattern of branching". Cell 87 (6): 1091-1101. PMID 8978613.
2. ^ Olsen SK, Garbi M. et al (2003). "Fibroblast growth factor (FGF) homologous factors share structural but not functional homology with FGFs". J. Biol. Chem. 278 (36): 34226-34236. PMID 12815063.
3. ^ Gospodarowicz D (1974). "Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on 3T3 cell growth". Nature 249 (453): 123-7. PMID 4364816.
4. ^ Arese M, Chen Y. et al (1999). "Nuclear activities of basic fibroblast growth factor: potentiation of low-serum growth mediated by natural or chimeric nuclear localization signals.". Mol. Biol. Cell 10 (5): 1429-1444. PMID 10233154.
5. ^ Böttcher RT, Niehrs C. (2005). "Fibroblast growth factor signaling during early vertebrate development". Endocr. Rev. 26 (1): 63-77. PMID 15689573.
6. ^ Amaya E, Musci T.J. and Kirschner M.W. (1991). "Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos". Cell 66 (2): 257-270. PMID 1649700.
7. ^ Borland C.Z., Schutzman J.L. and Stern M.J. (2001). "Fibroblast growth factor signaling in Caenorhabditis elegans". Bioessays 23 (12): 1120-1130. PMID 11746231.
8. ^ Coumoul X. and Deng C.X. (2003). "Roles of FGF receptors in mammalian development and congenital diseases". Birth Defects Res C Embryo Today 69 (4): 286-304. PMID 14745970.
9. ^ Sutherland D, Samakovlis C . and Krasnow M.A. (1996). "Branchless encodes a Drosophila FGF homolog that controls tracheal cell migration and the pattern of branching". Cell 87 (6): 1091-1101. PMID 8978613.
External links
Animal intercellular signaling peptides and proteins | |
|---|---|
| Growth factors | Epidermal growth factor - Fibroblast growth factor (FGF2) - Nerve growth factor - Platelet-derived growth factor - Transforming growth factor (TGFα, TGFβ, TGFβ pathway) |
| Other | Hedgehog (Sonic hedgehog) - Integrin - JAK/STAT (JAK/STAT) - MAPK/ERK pathway (MAPK/ERK) - NF-kB - Notch (Notch 1, Notch 3) - p53 - Wnt (Frzb) |
The term growth factor refers to a naturally occurring protein capable of stimulating cellular proliferation and cellular differentiation. Growth factors are important for regulating a variety of cellular processes.
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Wound healing, or wound repair, is the body's natural process of regenerating dermal and epidermal tissue. When an individual is wounded, a set of events takes place in a predictable fashion to repair the damage.
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Heparin, a highly sulfated glycosaminoglycan is widely used as an injectable anticoagulant and has the highest negative charge density of any known biological molecule.[1]
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Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (PG) in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins.
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Proteoglycans represent a special class of glycoproteins that are heavily glycosylated. They consist of a core protein with one or more covalently attached glycosaminoglycan chain(s).
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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, activated by second messengers resulting in
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Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as
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The fibroblast growth factor receptors are, as their name implies, receptors which bind to members of the fibroblast growth factor family of proteins.
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Structure
The fibroblast growth factor receptors consist of an extracellular ligand domain comprised of three..... Click the link for more information.
Basic fibroblast growth factor, also known as bFGF or FGF2, is a member of the fibroblast growth factor family.
In normal tissue, basic fibroblast growth factor is present in basement membranes and in the subendothelial extracellular matrix of blood
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In normal tissue, basic fibroblast growth factor is present in basement membranes and in the subendothelial extracellular matrix of blood
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The fibroblast growth factor receptors are, as their name implies, receptors which bind to members of the fibroblast growth factor family of proteins.
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Structure
The fibroblast growth factor receptors consist of an extracellular ligand domain comprised of three..... Click the link for more information.
Alternative splicing is the RNA splicing variation mechanism in which the exons of the primary gene transcript, the pre-mRNA, are separated and reconnected so as to produce alternative ribonucleotide arrangements.
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Bioassay is a shorthand commonly used term for biological assay and is a type of scientific experiment. Bioassays are typically conducted to measure the effects of a substance on a living organism . Bioassays may be qualitative or quantitative .
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A fibroblast is a type of cell that synthesizes and maintains the extracellular matrix of many animal tissues. Fibroblasts provide a structural framework (stroma) for many tissues, and play a critical role in wound healing.
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A fibroblast is a type of cell that synthesizes and maintains the extracellular matrix of many animal tissues. Fibroblasts provide a structural framework (stroma) for many tissues, and play a critical role in wound healing.
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The term cell growth is used in two different ways in biology.
When used in the context of reproduction of living cells the phrase "cell growth" is shorthand for the idea of "growth in cell populations by means of cell reproduction.
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When used in the context of reproduction of living cells the phrase "cell growth" is shorthand for the idea of "growth in cell populations by means of cell reproduction.
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ACID (Atomicity, Consistency, Isolation, Durability) is a set of properties that guarantee that database transactions are processed reliably. In the context of databases, a single logical operation on the data is called a transaction.
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Intracrine refers to a hormone that acts inside a cell. Steroid hormones act through intracellular (mostly nuclear) receptors and are thus considered as intracrines. In contrast, peptide or protein hormones generally act as endocrines, autocrines or paracrines by binding to their
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Heparin, a highly sulfated glycosaminoglycan is widely used as an injectable anticoagulant and has the highest negative charge density of any known biological molecule.[1]
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The term cell growth is used in two different ways in biology.
When used in the context of reproduction of living cells the phrase "cell growth" is shorthand for the idea of "growth in cell populations by means of cell reproduction.
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When used in the context of reproduction of living cells the phrase "cell growth" is shorthand for the idea of "growth in cell populations by means of cell reproduction.
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Bioassay is a shorthand commonly used term for biological assay and is a type of scientific experiment. Bioassays are typically conducted to measure the effects of a substance on a living organism . Bioassays may be qualitative or quantitative .
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endothelium is the thin layer of cells that line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. Endothelial cells line the entire circulatory system, from the heart to the smallest capillary.
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endothelium is the thin layer of cells that line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. Endothelial cells line the entire circulatory system, from the heart to the smallest capillary.
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Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. Though there has been some debate over this, vasculogenesis is the term used for spontaneous blood-vessel formation, and intussusception is the term for new blood vessel
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The blood vessels are part of the cardiovascular system and function to transport blood throughout the body. The most important types, arteries and veins, carry blood away from or towards the heart, respectively.
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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).
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In molecular biology, Platelet-derived growth factor (PDGF) is one of the numerous growth factors, or proteins that regulate cell growth and division. In particular, it plays a significant role in blood vessel formation (angiogenesis), the growth of blood vessels from
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Granulation tissue is the perfused, fibrous connective tissue that replaces a fibrin clot in healing wounds. Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size.
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The germ layer mesoderm forms in the embryos of animals more complex than cnidarians, making them triploblastic. Mesoderm forms during gastrulation when some of the cells migrating inward to form the endoderm form an additional layer between the endoderm and the ectoderm.
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Vertebrata
Cuvier, 1812
Classes and Clades
See below
Vertebrates are members of the subphylum Vertebrata (within the phylum Chordata), specifically, those chordates with backbones or spinal columns.
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Cuvier, 1812
Classes and Clades
See below
Vertebrates are members of the subphylum Vertebrata (within the phylum Chordata), specifically, those chordates with backbones or spinal columns.
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Invertebrate is an English word that describes any animal without a spinal column. The group includes 97% of all animal species — all animals except those in the Chordate subphylum Vertebrata (fish, reptiles, amphibians, birds and mammals).
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