Basic fibroblast growth factor
FGF2, also known as basic fibroblast growth factor (bFGF) and FGF-β, is a growth factor and signaling protein encoded by the FGF2 gene. It is synthesized primarily as a 155 amino acid polypeptide, resulting in an 18 kDa protein. However, there are four alternate start codons which provide N-terminal extensions of 41, 46, 55, or 133 amino acids, resulting in proteins of 22 kDa (196 aa total), 22.5 kDa (201 aa total), 24 kDa (210 aa total) and 34 kDa (288 aa total), respectively. Generally, the 155 aa/18 kDa low molecular weight (LMW) form is considered cytoplasmic and can be secreted from the cell, whereas the high molecular weight (HMW) forms are directed to the cell's nucleus.
Fibroblast growth factor protein was first purified in 1975, but soon afterwards others using different conditions isolated basic FGF, Heparin-binding growth factor-2, and Endothelial cell growth factor-2. Gene sequencing revealed that this group was in fact the same FGF2 protein and that it was a member of a family of FGF proteins. FGF2 binds to and exerts effects via specific fibroblast growth factor receptor (FGFR) proteins which themselves constitute a family of closely related molecules.
Like other FGF family members, basic fibroblast growth factor possess broad mitogenic and cell survival activities, and is involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion.
It has been hypothesized that, during both wound healing of normal tissues and tumor development, the action of heparan sulfate-degrading enzymes activates bFGF, thus mediating the formation of new blood vessels, a process known as angiogenesis.
In addition, it is synthesized and secreted by human adipocytes and the concentration of FGF2 correlates with the BMI in blood samples. It was also shown to act on preosteoblasts – in the form of an increased proliferation – after binding to fibroblast growth factor receptor 1 and activating phosphoinositide 3-kinase.
Recent evidence has shown that low levels of FGF2 play a key role in the incidence of excessive anxiety.
Additionally, FGF2 is a critical component of human embryonic stem cell culture medium; the growth factor is necessary for the cells to remain in an undifferentiated state, although the mechanisms by which it does this are poorly defined. It has been demonstrated to induce gremlin expression which in turn is known to inhibit the induction of differentiation by bone morphogenetic proteins. It is necessary in mouse-feeder cell dependent culture systems, as well as in feeder and serum-free culture systems. FGF2, in conjunction with BMP4, promote differentiation of stem cells to mesodermal lineages. After differentiation, BMP4 and FGF2 treated cells generally produce higher amounts of osteogenic and chondrogenic differentiation than untreated stem cells. However, a low concentration of bFGF (10 ng/mL) may exert an inhibitory effect on osteoblast differentiation.
- Anxiety disorders
- Fibroblast growth factor
- Growth factor
- Proteases in angiogenesis
- Receptor (biochemistry)
- Signal transduction
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- Basic+Fibroblast+Growth+Factor at the US National Library of Medicine Medical Subject Headings (MeSH)
- Human FGF2 genome location and FGF2 gene details page in the UCSC Genome Browser.